Characterization and quantification of cellular infiltrates in nasal mucosa of patients with grass pollen allergy, non-allergic patients with nasal polyps and controls.

Little is known about cellular infiltrates in nasal mucosa and the differences between these infiltrates in allergic and non-allergic patients. A reproducible and objective method making use of monoclonal antibodies for the quantification and characterization of cellular infiltrates in biopsy specimens of nasal mucosa is described. This method was used to study quantitative differences in cellular infiltrates in the epithelium and lamina propria of the nasal mucosa of patients with isolated grass pollen allergy, non-allergic patients with nasal polyps, and controls. A surprisingly wide variation was found in all groups. In all groups the T lymphocytes were much more numerous than the B lymphocytes. The number of CD8+ cells exceeded the number of CD4+ cells in the epithelium but in the lamina propria the numbers were approximately equal. Significant differences between the three groups were found with respect to the number of CD1+, IgE+, neutrophils and cytoplasmic IgG4+ cells. No significant differences were found in the numbers of CD4+, CD8+, CD14+, CD22+, HLA-DR+, IgG1-3+ cells or eosinophils. The use of biopsy in combination with monoclonal antibodies is an easy and well-tolerated method to study immunological reactions in the nasal mucosa. The results of this study indicate a possible role for a T-cell-mediated response in allergic rhinitis.     

Analysis of leucocyte subsets in the canine intestine

Immunohistochemistry and computer-aided morphometric analysis were used to define populations of leucocyte subsets in the intestinal tract of an outbred population of dogs with no evidence of gastrointestinal disease. In the small intestinal lamina propria, B cells and plasma cells (IgA+, IgM+ and IgG+) were prominent in peri-crypt regions, with a significant trend for a reduction in the number of cells towards the villous tip (P < 0.0001). By contrast, lamina propria T cells (CD3+) and T-cell subsets (CD4+ and CD8+) were present in greatest numbers at the tip of the villus, with significantly decreasing numbers towards the crypt regions (P < 0.0001). In the lamina propria, CD4+ cells outnumbered CD8+ cells (P = 0.05), but the opposite was true of the epithelial compartment (P < 0.001). The distribution of CD5+ lymphocytes was similar to that of CD3+ cells, in both the lamina propria and epithelial compartments. The numbers and distribution of cells expressing MHC class II, L1 and CD45 were recorded. Numerous eosinophils were present in the lamina propria, and an intra-epithelial population was also noted, especially in the crypt epithelium. Mast cells, which were mainly found in the subepithelial lamina propria, were also present within muscle layers, and cells expressing IgE had a similar distribution. Similar populations of cells were recorded in the colonic lamina propria and epithelium. The quantitative and qualitative data from this study will enable comparisons to be made with dogs suffering from inflammatory bowel diseases.     

Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T lymphocytes

Cryostat sections of histologically normal human colon were studied by double-label immunofluorescence techniques using a panel of monoclonal antibodies to T-lineage antigens and activation markers, with particular reference to the CD6 antigen. In the lamina propria, the majority population of T cells was of the CD3+, CD6+, CD4+ subset, of which virtually all were of the UCHL1+, CD45R-, Leu 8- phenotype of antigen-committed helper T cells. This majority lamina propria population did not express markers associated with blastogenesis (CD7), activation (MHC class II, CD25, CD38) or proliferation (OKT9, Ki67). In both intra-epithelial and lamina propria compartments, a subpopulation of CD3+ T cells was identified which did not express either the CD6 or CD5 peripheral 'pan T' markers. Most of the CD3+, CD6- cells were of the CD8+ (cytotoxic-suppressor) subset which co-expressed the CD7 antigen with a much higher frequency than did the CD6+ subpopulation. Expression of CD25, CD38 and HLA-D antigens, although infrequent, was confined to this CD8+, CD5-, CD6- population. Our data thus imply that the colonic mucosa is largely populated by mature, antigen-committed resting T cells of the helper-inducer phenotype.     

Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways

BACKGROUND: Allergic rhinitis (AR) and asthma are characterized by means of a similar inflammatory process in which eosinophils are important effector cells. The migration of eosinophils from the blood into the tissues is dependent on adhesion molecules. OBJECTIVE: To analyze the aspects of nasobronchial cross-talk, we studied the expression of adhesion molecules in nasal and bronchial mucosa after nasal allergen provocation (NP). METHODS: Nine nonasthmatic subjects with seasonal AR and 9 healthy control subjects underwent NP out of season. Bronchial and nasal biopsy specimens were taken before (T(0)) and 24 hours after NP (T(24)). Mucosal sections were analyzed for the presence of eosinophils, IL-5, eotaxin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and human endothelium (CD31). RESULTS: At T(24), an influx of eosinophils was detected in nasal epithelium (P =.01) and lamina propria (P <.01), as well as in bronchial epithelium (P =.05) and lamina propria (P <.05), of the patients with AR. At T(24), increased expression of ICAM-1, as well as increased percentages of ICAM-1+, VCAM-1+, and E-selectin+ vessels, were seen in nasal and bronchial tissue of patients with AR. The number of mucosal eosinophils correlated with the local expression of ICAM-1, E-selectin, and VCAM-1 in patients with AR. CONCLUSION: This study shows that NP in patients with AR results in generalized airway inflammation through upregulation of adhesion molecules.     

Stimulation of mucosal T cells in situ with anti-CD3 antibody: location of the activated T cells and their distribution within the mucosal micro-environment.

Mucosal T cells in explants of human fetal small intestine (17-20 weeks gestation) in organ culture were activated in situ using monoclonal anti-CD3 antibody. Changes in the distribution of T cells within the mucosa, and their phenotype, were monitored by immunohistochemistry on frozen sections. Anti-CD3 stimulated T cells (as determined by expression of CD25) were predominantly in the lamina propria and were rarely seen in the epithelium. In control cultures, after 72 h, CD3+ IEL decreased to low numbers compared to day zero. However, in cultures treated with anti-CD3, IEL numbers were maintained and in some experiments significantly increased compared to day zero levels. At onset of culture 50-60% of CD3+ IEL were CD4-, 8-, and virtually all were HML-1+. The T cell infiltrate into the epithelium induced by activation of lamina propria T cells with anti-CD3 was also mostly CD3+, 4-, 8-, HML-1+. These experiments provide strong evidence that increases in IEL numbers can be a consequence of lamina propria T cell activation.     

Distribution of beta 7 integrins in human intestinal mucosa and organized gut-associated lymphoid tissue.

Two alternative integrins involved in mucosal homing (alpha 4 beta 7) or epithelial retention (alpha E beta 7) of lymphocytes were examined in the human gut. The distribution of the beta 7 subunit [monoclonal antibody (mAb) M301] was bimodal in that it was strongly expressed by alpha E beta 7 + cells but weakly by alpha 4 beta 7 + cells. More than 90% of intraepithelial lymphocytes (IEL), including the minor subsets of CD4+, T-cell receptor (TCR) gamma/delta +, and CD3- cells, expressed alpha E beta 7 as did most lamina propria CD8+ (88%) and a fraction (36%) of CD4+ lymphocytes. Conversely, B-lineage cells (CD19+) and macrophages (CD68+) were negative. In gut-associated lymphoid tissue (GALT: Peyer's patches and appendix) only a few (< 5%) cells were positive for alpha E beta 7 (confined to CD8+ lymphocytes and CD11c+ putative dendritic cells). A relatively small fraction of IEL (30-50%) expressed alpha 4 beta 7 (mAb Act-1), while most (70%) lamina propria T and B lymphocytes, blasts, plasma cells and macrophages were positive. In GALT, T lymphocytes expressed similar levels of alpha 4 beta 7 as in the lamina propria whereas relatively few B lymphocytes (< 50%) were positive. Isolated lamina propria CD8+, CD4+, CD19+, and CD38+ cells contained mRNA for alpha 4 and the former three subsets as well as appendix CD8+ cells also for beta 7 while only lamina propria CD8+ cells had mRNA for alpha E. Together, the results suggested that alpha E beta 7 and alpha 4 beta 7 are differentially regulated in inductive sites and effector sites of the human gut. Because lymphoid cells at both sites expressed mainly alpha 4 beta 7, this integrin may be a homing receptor on memory and effector cells bound for lamina propria as well as on naive lymphocytes extravasating in GALT. Conversely, because alpha E beta 7 was mainly expressed by CD8+ cells in epithelium and lamina propria, it was probably induced after extravasation, in agreement with the observation that IEL and a fraction of lamina propria T lymphocytes (mainly CD8+ cells) generally expressed higher levels of beta 7 than most CD4+ and B cells. Also a subset of putative dendritic cells located near the follicle-associated epithelium of GALT expressed alpha E beta 7, perhaps reflecting epithelial interaction during primary immune responses.     

L-selectin expression differentiates T cells isolated from different lymphoid tissues in cattle but does not correlate with memory.

L-selectin (LECAM-1, LAM-1) was expressed by a high proportion of CD4+ and CD8+ T cells, as well as almost all of the gamma delta T-cell receptor (TcR)+ (WC1+) T cells, isolated from blood, lymph nodes or tonsils. CD4+ T cells in the lamina propria of the gut villi and CD8+ T cells in the villous epithelium as well as the majority of WC1+ T cells in the gut mucosa were L-selectin-. The proportion of T cells from Peyer's patches that synthesized the molecule was intermediate between the value for blood and gut mucosa. Expression of L-selectin therefore marks T cells in cattle with a distinct tissue distribution that correlates with its function as the peripheral node homing receptor. The proportion of CD4+ and CD8+ T cells in the circulation that were L-selectin+ decreased with age. Unlike CD45R, expression of L-selectin was not related to CD4 T-cell memory as judged by proliferation in transformation assays to soluble antigen. Three-colour immunofluorescent staining demonstrated four subpopulations of CD4 and CD8 T lymphocytes in peripheral blood mononuclear cells (PBMC) that were CD45R+, L-selectin+; CD45R+, L-selectin-; CD45R-, L-selectin+; CD45R-, L-selectin-. CD4(4) memory cells were CD45R- and L-selectin+ or L-selectin-. Taken with earlier studies the reported observations demonstrated that only one of the four phenotypes of the CD4+ T cells in blood is present in the lamina propria of the gut villi and these are CD45R-, L-selectin-. Two of the four phenotypes of CD8+ T cells were present in the gut epithelium; these were CD45R+, L-selectin- or CD45R-, L-selectin-. Expression of the bovine molecule was not rapidly down-regulated on T cells following activation by exposure to phorbol myristate acetate.     

The distribution of lymphocytes expressing alphabeta and gammadelta T-cell receptors, and the expression of mucosal addressin cell adhesion molecule-1 in the canine intestine.

The present study defined the distribution of alphabeta and gammadelta T-cell subsets, and the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the intestinal tract of an outbred population of dogs with no evidence of gastrointestinal disease. A panel of monoclonal antibodies reactive with the canine alphabeta and gammadelta T-cell receptors (TCRs) and human MAdCAM-1 was used in a series of immunoperoxidase or immunofluorescence studies. alphabeta T cells were predominant within the villous lamina propria with a significantly decreasing linear trend from upper villus to crypt (P<0.0001). A proportion of intraepithelial lymphocytes (IELs) also expressed the alphabeta T-cell receptor, with significantly greater numbers in villous than in crypt epithelium (P<0.0001). However, there were no significant differences in the numbers of either lamina propria or epithelial alphabeta T cells between different intestinal regions. gammadelta T cells were rare in the lamina propria, but a prominent gammadelta IEL population was present and shown by double-colour immunofluorescence studies to be principally of the CD4(&)minus;CD8alpha(&)minus; phenotype. MAdCAM-1 was expressed by endothelial cells in the mucosa, sub-mucosa and muscularis layers of all levels of the intestinal tract. In the mucosa, significantly more MAdCAM-1 positive endothelium was present in regions of crypt than villous lamina propria (P<0.0001), but there were no significant differences between expression in different intestinal regions. The quantitative and qualitative data will enable comparisons of these parameters to be made with those in dogs suffering from inflammatory bowel diseases.     

Human CD8+ intraepithelial T lymphocytes are mainly CD45RA-RB+ and show increased co-expression of CD45R0 in celiac disease

Expression of various CD45 isoforms (RA, RB and R0) on CD3+, CD4+ and CD8+ intraepithelial and lamina propria T cells was examined in situ by a three-color immunofluorescence technique in jejunal biopsy specimens from 32 patients with celiac disease and 18 controls. The median percentage of CD3+ intraepithelial lymphocytes (IEL) that expressed CD45R0 increased from 52% in controls to 69% in untreated celiac disease (p less than 0.01). Furthermore, the percentages of CD4+ and CD8+ IEL strongly positive for CD45R0 rose respectively from 94% and 24% in controls to 100% and 55% in untreated celiac disease. Conversely, CD45R0 was strongly expressed on most CD3+ lamina propria lymphocytes (LPL) both in control (81%) and diseased (77%-81%) mucosa. A variable fraction of the intraepithelial and lamina propria CD3+ T cells expressed mainly CD45RB (controls, 46% and 20%, respectively; celiac disease, 29% and 15%). Only 2% IEL and 4% LPL were positive for CD45RA. Expression of different CD45R isoforms thus identified three distinct CD8+ T cell subsets in human intestinal mucosa. In addition, our results suggested that antigen-primed CD8+CD45R0+ memory cells accumulate in the jejunal epithelium of patients with untreated celiac disease.     

Early HIV-1 target cells in human vaginal and ectocervical mucosa

After translocation through the pleuristratified epithelium of the lower female genital tract, HIV-1 encounters potential target mononuclear cells in the lamina propria of the vagina and ectocervix. Here we show that each major type of genital mononuclear cells, including dendritic cells (DCs), macrophages and lymphocytes, are susceptible to HIV-1 in vitro. Among suspensions of vaginal and ectocervical mononuclear cells, DCs were the first cells to take up virus, containing GFP-tagged virions as early as 15 min after exposure. At 2 hr after exposure, DCs still contained the largest proportion of HIV-1(+) cells compared to lamina propria macrophages and lymphocytes from the same mucosal compartment. By 4 days, however, lymphocytes from both vaginal and ectocervical mucosa supported the highest level of HIV-1 replication. Genital macrophages from the same mucosal tissues also were permissive to HIV-1, in sharp contrast to intestinal macrophages, which we have shown previously do not support HIV-1 replication. Thus, among human vaginal and ectocervical mononuclear target cells, DCs are the first to take up HIV-1 and T cells support the most robust viral replication. Further characterization of the parameters of HIV-1 infection in genital mononuclear cells will enhance our understanding of HIV-1 infection in the female genital tract.     

Immunohistochemical characterization of oral mucosal lesions in cats with chronic gingivostomatitis

Histological and immunohistochemical studies were performed on samples of the glossopalatine mucosa from 30 cats with feline chronic gingivostomatitis (FCGS). Immunohistochemical labelling and computer-assisted morphometric analysis were used to identify expression of CD3, CD4, CD8, CD79a, IgG, IgM, IgA, leucocyte antigen 1 (L1) and class II molecules of the major histocompatibility complex (MHC) in tissue sections. Mast cells were detected by toluidine blue staining. The microscopical lesions were graded by severity of inflammation and although this grading correlated significantly with the severity of mucosal inflammation assessed at clinical examination, sites assessed as clinically normal or mildly inflamed were poorly predictive of the histopathological grade in the corresponding tissue sample. The number of CD79a+ cells (mostly plasma cells), L1+ cells (mostly neutrophils) and CD3+ T cells, and the level of MHC class II expression, tended to correlate with the severity of the inflammation. In general, CD8+ T cells were more numerous than CD4+ T cells. The majority of the plasma cells were of the IgG isotype and fewer IgA+ and IgM+ plasma cells were present. In some cases MHC class II expression by mucosal epithelium, salivary duct epithelium or skeletal muscle fibres was observed. Relative to equivalent oral mucosal samples from healthy cats, the number of cells labelled for CD3, CD4, CD8, CD79a, IgG, IgM, IgA or L1, and the number of mast cells, within the lamina propria/submucosa were significantly increased. Limited analysis of the epithelial compartment also found more CD3+ T cells compared with healthy cats. These findings indicate that the glossopalatine mucosal lesions in FCGS represent a complex, chronic and destructive inflammatory process affecting the epithelium and lamina propria, with frequent extension into submucosal tissues. The predominance of CD8+ cells over CD4+ cells suggests the induction of an underlying cytotoxic cell-mediated immune response, which could be consistent with a viral aetiology.     

In vivo identification of Langerhans and related dendritic cells infected with HIV-1 subtype E in vaginal mucosa of asymptomatic patients.

In Thailand, the predominant HIV subtype is E, rather than Subtype B as in North America and Europe, and the predominant mode of transmission is heterosexual contact. Subtype E has the ability to replicate in vitro in Langerhans cells. We hypothesized that this cell type might constitute a reservoir for the HIV virus in vaginal mucosa of asymptomatic carriers. To examine this hypothesis, we compared vaginal tissue histology in HIV-1-seropositive cases with seronegative cases and determined the immunophenotype of HIV-1-infected cells, their numbers, and their distribution in vaginal mucosa. Vaginal biopsies were performed at four different sites from six asymptomatic HIV-1 Subtype E-infected persons and from six seronegative cases at necropsy and examined histologically. Immunophenotyping was performed using immunoperoxidase for Gag p24 HIV, CD3, CD20, CD68, CD1a, S-100 and p55 antigens and by double labeling, combining immunoperoxidase with alkaline phosphatase using pairs of the above antigens. Twenty of twenty-four vaginal biopsies (83.3%) from HIV-seropositive cases showed definite inflammation compared to five of twenty-four vaginal necropsies (20.8%) from HIV-seronegative cases. One third of HIV-seropositive biopsies (8/24) demonstrated p24-positive cells in the epithelium, whereas three-fourths (18/24) of the biopsies revealed p24-positive cells in the lamina propria. All seropositive patients showed positive cells in at least one biopsy, but not all biopsies contained positive cells. Infected cells were more frequently observed at sites of greater inflammation. The dendritic cell count in HIV-seropositive vaginal epithelium was significantly higher than that observed in the seronegative cases (P =.004). The majority of p24-positive cells in the vaginal epithelium were Langerhans cells (CD1a+/S-100+), whereas in the lamina propria, about half of p24-positive cells were Langerhans-related dendritic cells (p55+ and S-100+) and half were T lymphocytes. In conclusion, the increased propensity for heterosexual transmission of Subtype E may be related to vaginal inflammation, leading to the accumulation of Langerhans cells and related dendritic cells which, once infected with HIV, can act as a reservoir for further virus transmission.     

Lymphocyte phenotypes in the intestinal mucosa of sheep infected with Trichostrongylus colubriformis

Monoclonal antibodies to ovine lymphocyte surface antigens were used in an immunohistochemical study of the intestine of sheep. In the epithelium CD8+ cells predominated whereas the majority of lamina propria T lymphocytes were CD4+. Infection of sheep with the parasitic nematode Trichostrongylus colubriformis including sufficiently large numbers of parasites to induce protective immunity did not alter the number of CD4+ or CD8+ lymphocytes in the intestinal mucosa. In contrast, exposure of naive sheep to a single large infection of T. colubriformis resulted in a substantial decrease in number of CD8+ cells and moderate decreases in number of CD4+ cells in the duodenal but not the jejunal mucosa. MHC class II antigens were not detected either in or on epithelial cells of the sheep small intestine.     

The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques

A number of studies have shown that the ovarian hormone cycle affects genital tract immunoglobulin (Ig) levels and T cell function in both humans and rhesus monkeys. We hypothesized that shifts in immune cell populations occurring in response to hormone cycles are involved in the observed changes in genital tract immunity. To test this hypothesis, we characterized the type, number, and distribution of immune cells in the cervicovaginal mucosa at different stages of the menstrual cycle. Tissues from 18 normal female rhesus macaques were studied by immunohistochemistry and computerized morphometric analysis. The number and distribution of CD1a+ Langerhans' cells, CD2+, CD3+, CD4+, and CD8+ T cells, CD20+ B cells, and surface Ig+ plasma cells did not change in samples collected at the different stages of the cycle. However, in no relation to the stage of the menstrual cycle, the number of Langerhans' cells and other immune cell types was different in the various regions of the cervicovaginal mucosa examined. In addition, variation in thickness of the ectocervical and vaginal epithelium during a normal menstrual cycle of rhesus macaques is not accompanied by changes in intraepithelial immune cell populations. We conclude that steroid hormones do not influence genital mucosal immunity by changing the number or distribution of immune cells in the lower reproductive tract.     

Renal expression of intercellular adhesion molecule-1 in immunoglobulin A nephropathy: tubulointerstitial injury and prognosis

In immunoglobulin A nephropathy (IgAN), the abnormal expression of intercellular adhesion molecule-1 (ICAM-1) on proximal tubule epithelium is associated with the glomerular and interstitial infiltration of leucocytes, but its clinical significance remains uncertain. We analysed the relationship between the ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes, macrophages (CD14) and T lymphocytes (CD3) with the histologic features, proteinuria and serum creatinine at the time of renal biopsy and after 2.42 years in 45 patients with IgAN and after 1.8+/-1.5 years in 29 patients with non-glomerulonephritis (non-GN). In IgAN, ICAM-1+ tubule epithelium was 0.1+/-0.18 (x+/-SD), and this was associated with extracapillary proliferation (up to 20% of Bowman's space), glomerular sclerosis involving less than 50% of glomerular area, interstitial cellular infiltration, tubular atrophy and proteinuria level. ICAM-1+ interstitial leucocytes were correlated with glomerular sclerosis involving less than 50% of glomerular area, glomerular sclerosis involving more than 50% of glomerular area, tubular atrophy, interstitial fibrosis and serum creatinine level. In patients with an increase of 50% in serum creatinine, ICAM-1+, CD14+ and CD3+, interstitial leucocytes were significantly outnumbered than in patients with stable serum creatinine. In non-GN, ICAM-1+ tubule epithelium was 0.02+/-0.04 (U=344, P<0.05, vs IgAN), and this was inversely correlated with the percentage of the normal glomeruli and associated with glomerular sclerosis covering more than 50% of glomerular area, tubular atrophy and serum creatinine level. The association between tubular ICAM-1 and proteinuria and the association between interstitial ICAM-1+, CD14+ and CD3+, leucocytes and renal failure at presentation and the deterioration in IgAN in contrast with non-GN suggest that tubular and interstitial expression of ICAM-1 may be a marker of tubulointerstitial disturbance in IgAN.     

Local and systemic immune responses in murine Helicobacter felis active chronic gastritis.

Helicobacter felis inoculated per os into germfree mice and their conventional non-germfree counterparts caused a persistent chronic gastritis of approximately 1 year in duration. Mononuclear leukocytes were the predominant inflammatory cell throughout the study, although polymorphonuclear cell infiltrates were detected as well. Immunohistochemical analyses of gastric mucosa from H. felis-infected mice revealed the presence of mucosal B220+ cells coalescing into lymphoid follicles surrounded by aggregates of Thy-1.2+ T cells; CD4+, CD5+, and alpha beta T cells predominated in organized gastric mucosal and submucosal lymphoid tissue, and CD11b+ cells occurred frequently in the mucosa. Follicular B cells comprised immunoglobulin M+ (IgM+) and IgA+ cells. Numerous IgA-producing B cells were present in the gastric glands, the lamina propria, and gastric epithelium. Infected animals developed anti-H. felis serum IgM antibody responses up to 8 weeks postinfection and significant levels of IgG anti-H. felis antibody in serum, which remained elevated throughout the 50-week course of the study.     

The distribution of leucocyte subsets in the small intestine of healthy cats

The aim of this study was to investigate the distribution of leucocyte subsets in the small intestine of healthy adult cats (n=16). Immunohistochemical methods were used to identify leucocyte subsets within the mucosa of the duodenum, jejunum and ileum. Computer-aided morphometry was used to enumerate cells within the epithelial compartment, villous lamina propria and lamina propria adjacent to upper and lower crypt. Throughout the small intestine, IgA+ and IgM+ plasma cells were more prominent in the lamina propria adjacent to the lower crypt than in the villus, whereas IgG+ plasma cells were present in equal numbers in the crypt and villous regions. Overall, IgA+ plasma cells predominated and IgM+ plasma cells were higher in number than IgG+ plasma cells at each of the three anatomical locations. By contrast, T cells (CD3+) and T-cell subsets (CD4+ and CD8+) were present in greater numbers in the villous lamina propria than in the lamina adjacent to the crypts. Intraepithelial lymphocytes (IELs) were also characterized phenotypically, the majority being CD8+ T lymphocytes. Lamina propria macrophages and dendritic cells were characterized by expression of L1 and major histocompatibility complex (MHC) class II, and MHC class II expression by enterocytes overlying Peyer's patches, although rare, was also shown. The qualitative and quantitative data from this study provide a basis for comparison with cats with inflammatory enteropathies. Copyright Harcourt Publishers Ltd.     

Expression of adhesion molecules in human intestinal graft-versus-host disease.

The distribution of three cellular adhesion molecules, ICAM-1, ELAM-1 and VCAM-1, was studied in normal rectal mucosa and in graft-versus-host disease (GvHD) using immunohistological and morphometric techniques. In normal controls, ICAM-1 was demonstrable on endothelial cells and leucocytes within the lamina propria, ELAM-1 on endothelial cells only and VCAM-1 on lamina propria leucocytes, many of which exhibited long dendritic processes surrounding the glands. In GvHD, the enterocytes became positive for ICAM-1 and this was often associated with the presence of intra-epithelial LFA-1+ lymphocytes and macrophages, the latter containing debris of apoptotic cells. The staining was, however, restricted to the luminal membrane of the epithelial cells, raising doubts about the role of ICAM-1 as a ligand for LFA-1 on mucosal leucocytes in rectal GvHD. ELAM-1 expression was increased in GvHD both in terms of the length of positive endothelium and staining intensity. VACM-1 was increased on endothelial cells but not leucocytes in the lamina propria in contrast to our previous findings in cutaneous GvHD where VCAM-1+ dendritic cells were increased and endothelial cells remained negative. Normal patterns of adhesion molecule staining were seen in two biopsies exhibiting no morphological evidence of GvHD, from patients who had strong clinical evidence of the disease, indicating that immunostaining for these molecules is unlikely to be of help in improving the sensitivity of histological diagnosis. However, the possibility that adhesion molecule staining may be useful in improving diagnostic specificity by helping to distinguish GvHD from identical histological changes produced by irradiation and cytotoxic drugs is worthy of further investigation.     

Macrophage HIV-1 infection and the gastrointestinal tract reservoir

Excluding parenteral transmissions, virtually all vertical and homosexual transmission of human immunodeficiency virus type 1 (HIV-1) occurs via the gastrointestinal tract. Cellular routes implicated in the translocation of virus across the epithelium include M cells, dendritic cells, and epithelial cells. Intestinal epithelial cells express CCR5 and can selectively transfer CCR5-tropic HIV-1, the phenotype of the majority of transmitted viruses. In the lamina propria, virus encounters the largest reservoir of mononuclear cells in the body. Surprisingly, lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and support HIV-1 replication, implicating intestinal lymphocytes as the initial target cell in the intestinal mucosa. From the mucosa, virus is disseminated to systemic sites, followed by profound depletion of CD4+ T cells, first in the intestinal lamina propria and subsequently in the blood. As mucosal and circulating CD4+ T cells are depleted, monocytes and macrophages assume an increasingly important role as target and reservoir cells for HIV-1. Blood monocytes, including HIV-1-infected cells, are recruited to the mucosa, where they differentiate into lamina propria macrophages in the presence of stroma-derived factors. Although the prevalence of HIV-1-infected macrophages in the mucosa is low (0.06% of lamina propria mononuclear cells), the extraordinary size of the gastrointestinal mucosa imparts to intestinal macrophages a prominent role as a HIV-1 reservoir. Elucidating the immunobiology of mucosal HIV-1 infection is critical for understanding disease pathogenesis and ultimately for devising an effective mucosal HIV-1 vaccine.