Epithelial dendritic cells in pathological human oral tissues

Epithelial dendritic cells (EDC) were examined in human oral tissues with non-specific keratosis, lichen planus and squamous cell carcinoma. Acetone-fixed frozen sections were stained using an indirect immunoperoxidase technique and monoclonal antibodies to the human CD1 thymocyte (OKT6) and HLA-DR antigens. Significantly more T6⁺ and DR⁺ EDC were present in lichen planus tissues than normal controls, tissues with non–specific keratosis and the epithelia overlying/adjacent to squamous cell carcinomas, the latter tissues having comparable numbers of both T6⁺ and DR⁺ EDC. By contrast, significantly fewer T6⁺ EDC and significantly more DR⁺ cells were present in the invasive epithelium of squamous cell carcinomas than the overlying/adjacent epithelium of carcinomas, the non-specific keratosis group and the normal tissues. 23–60% of pathological tissues had either focal or general DR⁺ reactivity in keratinocytes, but there was no correlation between the density of T6⁺ or DR⁺ EDC and the keratinocyte DR status of the tissues. The results suggest that immunological enhancement occurs in lichen planus and possibly immunological impairment may characterize invasive squamous cell carcinoma.     

Inflammatory cell infiltrate associated with primary and transplanted tumours in an inbred model of oral carcinogenesis

This study characterised the nature of the local cellular immune responses associated with an inbred animal model of oral carcinogenesis. Inbred F344 rats developed moderately- to well-differentiated primary oral squamous cell carcinomas (SCC) after treatment with the carcinogen 4-nitroquinoline N-oxide (4-NQO) in vivo for 5–6 months. The inflammatory cell infiltrate associated with the primary tumours was predominantly of the macrophage lineage (CD45⁺, Ia⁺) and contained smaller numbers of CD8⁺ cells (NK cells, cytotoxic/suppressor T cells), CD5⁺ cells (T cells) and CD25⁺ cells (activated cells; T and NK cells). Keratinocyte cell lines were established from three lingual and one palatal SCC. By contrast to normal keratinocytes, tumour-derived cell lines were immortal and independent of 3T3 fibroblast support. All of the tumour-derived cell lines were tumorigenic in athymic ( nu/nu ) mice and showed contrasting latent periods of tumour development and histological differentiation; normal keratinocyte grafts were non-tumorigenic in athymic mice. Three of four malignant cell lines formed well-differentiated tumours in syngeneic F344 rats; the tumours regressed after 10–14 days. Regressing grafts contained significantly larger numbers of NK cells (CD5^-, CD8⁺) in the inflammatory cell infiltrate compared with that associated with primary tumours (p<0.04). One malignant cell line and normal keratinocytes were non-tumorigenic in syngeneic hosts. The results demonstrate phenotypic variation in the cell-mediated immune responses associated with the actively growing primary SCC and the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumour rejection in this model.     

Oral mucosal lesions in experimental graft-versus-host disease: morphological and immunohistochemical characterization of infiltrating cells

To facilitate recognition of the oral mucosal lesion that develops in rats with graft-versus-host disease (GVHD) induced by injecting spleen cells of parental strain rats (Brown Norway) into non-irradiated (Brown Nonvay×Lewis) F1 hybrid rats, we followed the development of the tongue lesion histologically and immunohistochemically. This assessment revealed an increase in the number of MHC class II⁺ cells with dendritic shape in the lamina propria to be the earliest stage of the tongue lesions in GVHD rats. The subsequent mononuclear cell infiltration with epithelial cell destruction, characteristic of GVHD. consisted of CD8⁺ cells and macrophages. Our findings seem to indicate that MHC class II⁺ cells with dendritic shape may provide antigen presentation in the induction of local immunological responses, including tissue destruction, by CD8⁺ cells and macrophages in the tongue of GVHD rats.     

Cellular immune correlates of clinical severity in oral lichen planus: preliminary association with mood states

OBJECTIVES: We investigated cellular immune and psycho-immune dysfunctions in patients with erosive and non-erosive oral lichen planus (OLP) lesions.
METHODS: Patients with erosive or non-erosive OLP were screened at the UCLA Dental Clinic. The profile of mood states (POMS) was administered. T lymphocyte subpopulations were monitored by dual fluorescence. T lymphocytes were stimulated with phytohemagglutinin (PHA) for assessment of markers of activation by flow cytometry and of interleukin (IL)-2 production by ELISA.Plasma cortisol and neopterin levels were assessed by radioimmunoassay.
RESULTS: Circulating T cells that express the cluster of differentiation no.4 (CD4⁺) but devoid of the CD45RA marker, and POMS score were significantly associated ( r = 0.83, P < 0.05) in the patients we studied. We found a significantly higher ( P < 0.05) per cent and absolute lymphocyte numbers of circulating CD4+CD45RA cells in the OLP patients with erosive lesions, compared to OLP patients with non-erosive lesions. The ratio of CD4⁺ CD45RA⁺ over CD4+CD45RA cells was significantly ( P < 0.05) biased toward the CD4+CD45RA subpopulation in OLP patients with erosive lesions (ratio = 0.19 ± 0.09) compared to patients with non-erosive OLP lesions (ratio = 0.47 ± 0.15). The expression of CD54, but not that of CD69, was significantly blunted ( P < 0.05) in OLP patients following CD3⁺ cell stimulation. IL-2 production and plasma neopterin were normal in these patients. There was no correlation between plasma cortisol and T cell populationS. CONCLUSIONS: We find fine differences in psycho-immune interactions between patients afflicted with non-erosive OLP lesions compared to those with erosive OLP lesions.     

High numbers of T cells in gingiva from patients with human immunodeficiency virus (HIV) infection

A quantitative, immunohistologic evaluation of CD3⁺, CD4⁺and CD8⁺ cells was carried out on gingival biopsies from 25 HIV-infected persons with gingivitis or periodontitis and 13 HIV-seronegative persons with periodontitis. CD3⁺ T cells were found in all biopsies. CD8⁺ cells were significantly more numerous and the CD4⁺/CD8⁺ ratio was significantly decreased in the gingival connective tissue of the HIV⁺ patients (P < 0.05). The number of CD4⁺ lymphocytes subjacent to the pocket epithelium was moderately lower in the HIVH patients as compared to the HIV⁺ patients (P < 0.05). HIV⁺ patients with a history of necrotizing periodontal disease had fewer CD4⁺ cells subjacent to the oral gingival epithelium than patients without such disease (P < 0.05). The general HIV-related changes in T lymphocyte numbers were therefore reflected in inflamed gingival tissues. HIV⁺ patients had, however, significantly higher CD4⁺/CD8⁺ ratios in gingiva than in peripheral blood (P < 0.05), indicating that CD4⁺ T cells are actively recruited to gingiva, even in cases of extreme CD4⁺ T lymphocytopenia.     

Expression of CD1 and HLA-DR by Langerhans cells (LC) in oral lichenoid drug eruptions (IDE) and idiopathic oral lichen planus (LP)

Numbers of Langerhans ceils (LC) expressing the common thymocyte antigen (T6/CD1) are similar in oral lichen planus (LP) and in normal oral epithelium: however, expression of class II major histocompatibility antigens (HLA-DR/Ia) by Langerhans cells is greater in lichen planus than in normal epithelium, a phenomenon believed to be associated with activation and antigen presentation. This study quantified the numbers of T6+ve and HLA-DR + ve Langerhans cells in oral lichen planus and lichenoid drug eruptions (LDE) to investigate whether differences may reflect differing routes of antigen presentation. Six patients with oral lichenoid drug eruptions and six control idiopathic oral lichen planus patients had lesional biopsies. An immunoperoxidase technique was used to demonstrate binding of T6 and HLA-DR antibodies to identify dendritic intra-epithelia! cells as Langerhans cells and activated Langerhans cells, respectively. In lichenoid drug eruptions, the number of HLA-DR+ve LC was significantly lower than the number of T6+ve LC ( P < 0.05), whereas in idiopathic lichen planus the numbers of T6+ve and HLA-DR+ve LC did not differ significantly ( P = 0.20). The results provide evidence for differences in the routes of antigen presentation in lichenoid drug eruptions and idiopathic lichen planus.     

Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus

This study has addressed the question of whether there is selective recruitment and distribution of intra-epithelial leucocytes in lesions of oral lichen planus (OLP). T-lymphocyte subsets were examined in the epithelium and peripheral blood of patients and controls using flow cytometry and double immunofluorescence, and the relationship between keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression with T-lymphocyte and Langerhans cell (LC) distribution was examined. The circulating 'memory'subset (CD45RO⁺) of T-helper cells (CD4⁺) was increased from 49.1% in controls to 65.7% in patients ( P = 0.005), while the 'naive'subset (CD45RA⁺), which was absent from control epithelium, comprised 24% of helper cells in OLP ( P =0.037) and all T-cell and LC counts were significantly raised in ICAM-1-expressing areas of epithelium. These data demonstrate changes in intra-epithelial T-lymphocyte and LC populations compared with normal oral mucosa and suggest there is selective recruitment in OLP. In addition, Keratinocyte ICAM-1 expression does appear to be associated with accumulation of infiltrating T lymphocytes and LC.     

Significance of oral examination in chronic graft-versus-host disease

Fourteen patients who received allogeneic bone marrow transplantation (BMT) were examined 100 to 220 days after BMT. Ten out of 14 patients were diagnosed as having chronic graft-versus-host disease (cGVHD) in skin, liver, eyes and other organs. These cGVHD patients also had objective evidence of oral involvement. Subjective xerostomia was experienced by 7 cGVHD patients and decreased whole saliva flow was observed in 4 cGVHD patients. However, no patient had a history of parotid swelling or notable abnormality in parotid sialography. Labial salivary glands (LSG) of 9 cGVHD patients showed atrophy and/or destruction in association with diffusely infiltrating lymphocytes. The infiltrating lymphocytes were mainly CD3⁺ T cells with a predominance of CD8⁺ cells over CD4⁺ cells. Lichenoid lesions on the oral mucosa were also observed in 5 cGVHD patients. Thus, this study indicated that oral examination, including LSG biopsy, is useful in the diagnosis of cGVHD.     

FOXP3+ T regulatory cells in lesions of oral lichen planus correlated with disease activity

Objective:  The aim of this study was to determine the correlation between the number of FOXP3⁺ T cell in lesions and the disease activity of patients with oral lichen planus (OLP).
Materials and Methods:  The expression of FOXP3 was investigated using immunohistochemical staining and real-time RT-PCR in 23 OLP lesions and 12 controls. Changes of FOXP3⁺ Treg in peripheral blood from three patients' pre and post-treatment were assessed using flow cytometry.
Results:  Few FOXP3⁺ cells were detected in controls, but an increased number of FOXP3⁺ cells were observed in lesions ( n  = 20, 40.99 ± 24.68 cells per high-power field – hpf). Furthermore, the frequency of FOXP3⁺ Treg in reticular OLP ( n  = 7, 63.6 ± 23.2 cells per hpf) was significantly higher than that in erythematous/erosive OLP ( n  = 13, 28.8 ± 16.8 cells per hpf, P  = 0.001). In addition, negative correlation was found between the number of FOXP3⁺ Treg and disease activity (correlation oefficient = −0.557, P  = 0.013). The proportion of FOXP3⁺ Treg showed remarkable increase in peripheral blood from patients after treatment (1.39 ± 0.71% vs 4.91 ± 1.59%).
Conclusions:  These data indicated that FOXP3⁺ Treg were involved in the pathogenesis of OLP and correlated with disease's subtype and activity.     

Extent and diversity of inflammatory cell infiltrates in squamous cell carcinomas and basal cell epitheliomas of the head and neck

Using monoclonal antibodies reactive with Langerhans' cells (LCs), macrophages, and T cell subpopulations, the density and proportions of cells of the immune system of the normal oral mucosa were determined immunohistochemically, and compared with findings in oral squamous cell carcinomas (SCC) and basal cell epitheliomas (BCE). In normal oral epithelia, the dominant cell type was the LC, positive for CD 1, and expressing HLA-DR antigens (DR⁺). Many intraepithelial cells were lymphocytes of the suppressor/cytotoxic phenotype (CD 8⁺), which was also the most prominent cell type in the normal mueosal slroma. Significant differences were observed for the content of CD 8-, OKM 1-, and CD 4-positive cells in the epithelium of normal oral mucosa, SCC, and BCE, and for the amount of CD 1-positive Langerhans cells in the connective tissue of the different groups of tissues. When CD 4/CD 8 ratios were calculated, differences between SCC and BCE became most evident. A CD 4/CD 8 ratio greater 0.5 was seen to be characteristic for BCE. Thus, in contrast to the striking preponderance of suppressor/cytotoxic lymphocytes (CD 8⁺) in SCC, BCE showed typically almost balanced numbers of suppressor/cytotoxic (CD 8⁺) and helper/induced (CD 4⁺) lymphocytes. This finding further underlines the biological differences recognized between these most common neoplasias of the head and neck.     

Increased number of CD25+ FoxP3+ regulatory T cells in oral squamous cell carcinomas detected by chromogenic immunohistochemical double staining

Background:  The role of tumor-infiltrating regulatory T cells (Treg) compromising antitumor effects of immune cells in oral squamous cell carcinoma (OSCC) is largely unknown.
Purpose:  The presence of CD25⁺ FoxP3⁺ Treg as well as of CD3⁺ FoxP3⁺ and of CD8⁺ FoxP3⁺ tumor-infiltrating lymphocytes (TIL) was verified in OSCC and compared with non-cancerous lymphoepithelial tissue.
Method:  Three double stainings (CD3/FoxP3, CD8/FoxP3 and CD25/FoxP3) were performed on tissue sections of 15 OSCC and compared with 15 human tonsils.
Results:  OSCC biopsy samples provide evidence for a strong infiltration of TIL, in particular, naturally occurring CD25⁺ FoxP3⁺ Treg. Whereas a comparison of OSCC and control tissue did not show significant changes in the number of CD3⁺ FoxP3⁺ TIL and of CD8⁺ FoxP3⁺ TIL, a significantly higher frequency of CD25⁺ FoxP3⁺ TIL (Treg) could be observed in OSCC ( P  < 0.001, two-sided t -test). Given the small number of specimens, a significant correlation with tumor stage could not be verified.
Conclusion:  Chromogenic double staining of CD4/FoxP3 is a promising tool for the detection of Treg in paraffin-embedded tissue of OSCC.     

Oral lichen planus: A disease or a spectrum of tissue reactions? Types,causes, diagnostic algorhythms,prognosis, management strategies

Oral lichen planus and lichenoid lesions comprise a group of disorders of the oral mucosa that likely represent a common reaction pattern to 1 or more unknown antigens. The coexistence of hyperkeratotic striation/reticulation, varying degrees of mucosal inflammation from mild erythema to severe widespread ulceration, and a band‐like infiltrate of mononuclear inflammatory cells including activated T lymphocytes, macrophages, and dendritic cells, are considered suggestive of oral lichen planus and lichenoid lesions. Several classification systems of oral lichen planus and lichenoid lesions have been attempted, although none seem to be comprehensive. In this paper, we present a classification of oral lichen planus and lichenoid lesions that includes oral lichen planus, oral lichenoid contact lesions, oral lichenoid drug reactions, oral lichenoid lesions of graft vs. host disease, discoid lupus erythematosus, and systemic lupus erythematosus, lichen planus‐like variant of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, chronic ulcerative stomatitis, lichen planus pemphigoides, solitary fixed drug eruptions, and lichen sclerosus. We present the clinical and diagnostic aspects of oral lichen planus and lichenoid lesions, and discuss related treatment options.     

Immunoelectron microscopic study of distribution of T cell subsets in oral lichen planus

Abstract – Monoclonal anti-CD4, anti-CD8, and anti-GD18 antibodies were applied in avidinbiotin-peroxidase complex staining using a pre-embedding immunoelectron microscopy technique. Although most of the local T cells in situ were of CD4⁺ subtype, local CD8⁺ cells generally had a lower nucleus/cytoplasm ratio and contained more cell organelles than CD4⁺ cells. This suggests a local activation of CD8⁺ subpopulation, rather than activation of the numerically predominant CD4⁺ cells. Topographical analysis disclosed that all lymphocytes, regardless of location, were CD18⁺ and that most of the CD8 ⁺ cells were located subbasally and intraepithelially, whereas CD4⁺ cells often occurred in small clusters deeper down in the subepithelial lymphocyte-rich band. Furthermore, CD8⁺ cells were often in close contact with macrophages, whereas CD4⁺ cells were in some instances in direct contact with plasma cells. This indicates that CD4⁺ cells may be involved in T cell-dependent B cell-mediated immunoglobulin synthesis, whereas CD8⁺ cytotoxic lymphocytes and tissue macrophages may be involved in the local pathogenetic process leading to basement membrane alterations.     

Oral ulcers in HIV-positive Peruvian patients: an immunohistochemical and in situ hybridization study

Background:  This study describes the histopathological, immunohistochemical (IHC) and in situ hybridization (ISH) data of 25 cases of oral ulcers in HIV-positive patients, with clinical and microscopical features similar to ulcers not otherwise specified (NOS)/necrotizing ulcerative stomatitis (NUS).
Methods:  Sex, age and clinical history were obtained from the clinical records. Histological analysis for H&E, Gomori–Grocott and Ziehl–Neelsen stains, IHC analysis to detect infectious agents and to characterize inflammatory cellular infiltrate, and ISH for cytomegalovirus (CMV) and EBER1/2 were performed.
Results:  Twenty-one patients were men and four were women (mean age of 34.6 years). The tongue was preferentially affected. Microscopically, the lesions showed extensive necrosis, leukocytoclasia, vasculitis with luminal fibrin clots and an intense inflammatory cellular infiltrate predominated by CD68⁺ atypical large cells, normal-sized and crescent-shaped nuclei macrophages, interspersed by CD8⁺ T lymphocytes. Mast cells were also observed in all samples studied. CD4⁺ T lymphocytes, CD20⁺ B lymphocytes and VS38c⁺ plasma cells were practically absent. CMV and EBER1/2 were identified in scarce cells of 3 and 16 of 25 cases respectively.
Conclusion:  These results show that CD68⁺ macrophages, followed by CD8⁺ T lymphocytes, were the predominant inflammatory cells, indicating they are relevant to the pathogenesis of the ulcers, possibly reflecting an abnormal immune response in the oral mucosa. The clinicopathological and immunoprofile features of the present cases are similar to NOS ulcers/NUS in HIV-positive patients.     

The changes in the T-lymphocyte subsets in a population of Turkish children with puberty gingivitis

Objective.   The aim of the study was to investigate the number of CD4 and CD8 T lymphocytes, analyse subjects with gingivitis and those without, and determine the role of T lymphocytes in the pathobiology of puberty gingivitis.
Material and methods.   Fifty individuals with and without puberty gingivitis were recruited for this study. The CD4⁺ and CD8⁺ T-lymphocyte counts were determined using flow cytometry on the biopsy samples, and the CD4⁺/CD8⁺ ratio was calculated. At the same time, periodontal index scores were recorded to assess the periodontal status. Acquired data were analysed statistically using a paired t -test to compare laboratory values obtained before and after the treatment in individuals with puberty gingivitis and disease-free individuals. In addition, Pearson's correlation analysis was performed to investigate the relation between laboratory values and clinical measurements.
Results.   The CD4⁺/CD8 ratio in gingival tissues obtained from test group was significantly higher ( P <  0.05) than that found in the gingival tissue obtained from control group. We found that the CD4⁺ and CD8⁺ lymphocyte counts continued to increase significantly ( P <  0.001) and the CD4⁺/CD8⁺ ratio continued to drop significantly ( P <  0.05) after treatment in test group.
Conclusions.   T lymphocytes could play a significant role in the pathobiology of puberty gingivitis     

Immunocompetent cells in oral candidiasis of HIV-infected patients: an immunohistochemical and electron microscopical study

OBJECTIVE: The purpose of this study was to elucidate the pathogenesis of oral candidiasis, a common cause of discomfort and social impairment among HIV-infected individuals.
STUDY DESIGN, MATERIALS AND METHODS: The oral mucosal immune system cells were analysed by immunohistochemistry and electron microscopy in biopsies from five erythematous and four pseudomem-branous candidiasis cases and were compared with those from seven HIV-positive and 10 HIV-negative controls without candidiasis.
RESULTS: The superficial lamina propria and basal epithelial layer was populated by CD1a⁺ Langerhans cells with infiltration of CD8⁺ lymphocyteS. Within the submu-cosa are CD36⁺ dendritic macrophages and lymphocytes, although CD4⁺ subsets were absent from the infiltrate. The expression of human leukocyte antigen system, DR locus (HLA-DR) and leukocyte specific adhesion molecules was low in erythematous, yet more marked in pseudomembranous candidiasiS. In the pseudomembra-nous form, CD14⁺ leukocytes were found in the basal epithelial layer. Langerhans cells were significantly more numerous and were richer in dendrites and Birbeck granules in erythematous than in pseudomembranous can-didiasis.
CONCLUSIONS: Candidiasis is associated with alterations in the number and differentiation of lymphocytes and dendritic cells, being more severe in the pseudo-membranous than erythematous form. We propose that these alterations play a role in the pathogenesis and evolution of the disease.     

A comparative immunological analysis of the oral mucosa in chronic graft-versus-host disease and oral lichen planus.

Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic graft-versus-host disease (GVHD) involving the mouth were compared with biopsies taken before transplantation. They were also compared with biopsies from otherwise healthy patients with oral lichen planus, and with those from a control group of normal individuals. Biopsies from chronic GVHD exhibited a low number of infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen planus, which showed intense cell infiltration (p less than 0.005). The ratio of CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD exhibited no consistent variation compared with those taken before transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all groups investigated varied between 4:1 and 6:1. The number of natural killer cells (CD57), was increased in biopsy specimens taken before transplantation compared with the other groups. The frequency of homing receptor, Leu-8 bearing T cells was low in the biopsy specimens of all groups, compared with the corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the number of lymphocytes with transferrin receptors was increased compared with the pretransplant and control groups. Virtually no infiltrating cells were carrying interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells (CD1) were more frequently found in the specimens from chronic GVHD and oral lichen planus than in the pretransplant specimens and the control group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

US8Xerostomia

The lichenoid reactions are one of the most prevalent pathological reaction patterns of the oral mucosa. Oral lichen planus (OLP), lichenoid contact reactions (LCR) and graft-versus-host disease belong to this group of lichenoid reactions. Apart from a common clinical appearance, these disorders cannot be discriminated from each other by the use of histopathological techniques. New knowledge about the etiology behind LCR and GvHD can also, to some extent, be extrapolated to the immune mechanisms, which participate in the pathogeneses of OLP. Besides a discussion on different etiological aspects of OLP, this presentation will focus on treatment strategies used to manage lichenoid reactions. During recent years a debate has been conducted on the malignant potential of lichenoid reactions.     

Two cases of tongue cancer treated with intra- and peri-tumoral injection of recombinant interleukin-2 alone: immunohistochemical considerations to clinical tumor response

SUBJECTS AND METHODS: Two cases with stage II tongue cancer who exhibited different responses to intra-and peri-tumoral administration of rlL-2 alone are presented. Special consideration is given to the relationship between tumor responses to rlL-2 and clinicopatholog-ical and immunohistopathological findings.
RESULTS: The patient who responded completely to treatment showed an exophytic tumor growth pattern, low-grade cancer invasion, and predominant infiltration of CD8⁺ lymphocytes over CD4⁺ lymphocytes in cancer cell nests. The non-responder showed endophytic tumor growth, high-grade cancer invasion, and uniform distribution of both CD4⁺ and CD8⁺ lymphocytes in cancer cell nests.
CONCLUSIONS: Distribution of adequate amounts of T lymphocytes subsets may be necessary in order for good tumor response to biotherapy with rlL-2; other clinical and histopathological variables predicting the effect for cancer chemotherapy remain to be identified.     

Systemic treatment of anti-CD4+CD25+ T cell monoclonal antibody exacerbates sialoadenitis in submandibular glands during the early life in lupus-prone female NZB × NZWF1 mice

Background:  The maintenance mechanisms of peripheral tolerance by CD4⁺CD25⁺ T cells before the development of sialoadenitis in secondary Sjögren's syndrome (sSS) are not well understood. The aim of the present study is to examine the effect of reduction of CD4⁺CD25⁺ T cells on the development of sialoadenitis during the early life in female NZB × NZWF₁ (B/WF₁) mice, a model for human sSS.
Methods:  Female B/WF₁ mice at 3 days after birth were treated with either anti-mouse CD4⁺CD25⁺ T cells rat IgG₁ monoclonal antibody (mAb) or Rat IgG₁(control). At 25 weeks of age, autoantibodies against nucleus and cytoplasm of ductal epithelial and myoepithelial cells, and histpathology of submandibular glands were examined in the mAb-treated and control groups. Also the development of anti-Ro/SS-A antibodies was examined until 25 weeks of age in both groups.
Results:  The mAb-treated group showed severe lesions with the development of autoantibodies compared to the control group.
Conclusions:  The present results suggest that peripheral CD4⁺CD25⁺ T cells may, at least in part, contribute to down-regulate the development of sialoadenitis in submandibular glands of lupus-prone female B/WF₁ mice during their early life.