High endothelial differentiation in human lymphoid and inflammatory tissues defined by monoclonal antibody HECA-452.

Lymphocyte traffic into lymph nodes and into mucosa-associated lymphoid tissues is regulated by specialized postcapillary high endothelial venules (HEVs). The authors have produced a rat monoclonal antibody, HECA-452, that detects a human endothelial cell differentiation antigen selectively expressed on high endothelium. In immunoperoxidase studies, HECA-452 intensely stains all HEVs within lymphoid organs. In normal nonlymphoid tissues the antibody stains no vascular endothelium. The antibody, in addition to reacting with high endothelium, cross-reacts with a set of monocytic cells. In pathologic states such as autoimmune thyroiditis and Crohn's disease, known for the development of dense, frequently organized, lymphocytic infiltrates, HECA-452 detects HEV-like vessels containing luminal and intramural lymphocytes, presumably in the process of extravasating. The antigen was not expressed at detectable levels by venules in less heavily infiltrated chronic inflammatory sites nor in acutely inflamed tissues. In lymphoid malignancies, the only vessels stained were morphologically characteristic HEVs in association with areas of residual normal lymphoid tissue or reactive lymphocytic infiltrates. The specificity of HECA-452 for high endothelial cells confirms the highly specialized nature of these vessels and will permit studies of the regulation of high endothelial cell differentiation in vivo and in vitro. The HECA-452 antigen is preserved in paraffin sections of sublimate formaldehyde- and also routinely formalin-fixed tissues. Thus, HECA-452 will be widely applicable for the immunohistologic detection of endothelium specialized for the support of highly increased lymphocyte extravasation in inflammatory sites.     

“Nk-Like” T Cytotoxicity Against B Lymphocytes in a Hypogammaglobulinemic Patient

Physiologically, cells with NK activity appear to exert a negative control on immunoglobulin production. The clinical association of large granular lymphocyte (LGL) proliferation with hypogammaglobulinemia suggests that these functional NK cells could also be involved in pathological situations.

We studied in vitro lymphocyte functions in a patient presenting LGL proliferation associated with hypogammaglobulinemia. The CD3⁺ CD8⁺ CD57⁺ CD16^- phenotype lymphocytes expressed a high NK type cytotoxicity towards K562 targets, suggesting that they may be considered as “NK-like” T cells. We cultured the patient peripheral blood mononuclear cells (PBMC) with control subject PBMC and with PBMC from two other subjects with B chronic lymphocytic leukemia (B- CLL) of the CD20⁺ CD21^- CD10^- phenotype. Patient PBMC exhibited a lytic activity on control PBMC and on the B lymphocytes of one of the two B- CLL but only in the presence of PWM. This activity was not exerted by the culture supernatant and required a cell - to - cell contact. We suggest that the hypogammaglobulinemia observed in this patient may be related to a cytotoxic effect exerted on B lymphocytes by a CD3⁺ CD8⁺ CD57⁺ CD16^- LGL proliferation.     

The ontogeny of human lymphocyte recirculation: high endothelial cell antigen (HECA-452) and CD44 homing receptor expression in the development of the immune system

In the present report we have studied the expression of a lymphocyte homing receptor, the CD44 antigen, and of HECA-452, a high endothelial-specific antigen, during the development of the human immune system. We found that prothymocyte immigrants of the thymus already expressed the CD44 antigen. Similarly, the first peripheral T lymphocytes in fetal lymph nodes, tonsils and gut-associated lymphoid tissue were also CD44+. Cortical thymocytes and germinal center cells were CD44-. CD44 antigen expression was, thus, not limited to mature recirculating lymphocytes. This suggests that CD44 may not only be involved in recirculation of mature lymphocytes but also in the migration of prothymocytes to their site of maturation, i.e. the thymus. High endothelial venules (HEV) were not demonstrable at the early onset of lymphocyte immigration into the developing lymphoid organs. However, when large-scale influx of lymphocytes occurred, it paralleled HEV development. HECA-452 antigen expression preceded the morphological transformation of endothelium into a HEV phenotype. Expression of this antigen therefore, independently reflected the specialized nature of high endothelium. In a patient with complete DiGeorge's syndrome normal HEV developed, indicating that the presence of T lymphocytes is not a requirement for HEV development. Interestingly, a subpopulation of venules located in the thymic medulla near the cortico-medullary junction expressed the HECA-452 antigen. These vessels, which had flat or intermediately high endothelium, are probably involved in lymphocyte migration to the thymus.     

Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets

The induction of antigen-specific tolerance is critical for maintaining immune homeostasis and preventing autoimmunity. Because the central tolerance that eliminates potentially harmful autoreactive T cells is incomplete, peripheral mechanisms for suppressing self-reactive T cells play an important role. Dendritic cells (DCs) are professional antigen-presenting cells, which have an extraordinary capacity to stimulate naïve T cells and initiate primary immune responses. Recent accumulating evidence indicates that several subsets of human DCs also play a critical role in the induction of peripheral tolerance by anergizing effector CD4⁺ and CD8⁺ T cells or by inducing the differentiation of naïve T cells into T-regulatory cells, which produce interleukin (IL)-10. Human DC subsets with the property of suppressing an antigen-specific T-cell response include plasmacytoid DCs, which are either in an immature state or in a mature state induced by CD40 ligand stimulation, and monocyte-derived DCs, which are either in an immature state or have had their state modulated by treatment with IL-10 or CD8⁺CD28⁻ T cells. These “tolerogenic” DCs may be relevant to therapeutic applications for autoimmune and allergic diseases as well as organ transplant rejection.     

Differential expression of the HECA-452 antigen (cutaneous lymphocyte associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas

The monoclonal antibody HECA-452 identifies an antigen that is primarily expressed on high endothelial venules, the preferred site of lymphocyte extravasation in lymphoid tissues, and also on a subpopulation of myelomonocytic cells and some T-cells. We investigated the expression of the HECA-452 antigen, also called the cutaneous lymphocyte associated antigen, in primary cutaneous and primary non-cutaneous T-cell non-Hodgkin's lymphomas. The tumour cells of cutaneous T-cell non-Hodgkin's lymphomas were positive in 53% of cases, while only 5% of the non-cutaneous lymphomas were positive. These differences were also present in morphologically identical tumours. Thus, the tumour cells in six out of 10 primary cutaneous anaplastic large cell T-cell lymphomas were positive, while they were positive in none of 24 primary non-cutaneous anaplastic large cell T-cell lymphomas. In general, primary cutaneous and primary nasal T-cell non-Hodgkin's lymphomas were devoid of HECA-452 positive high endothelial venules, whereas most nodal T-cell non-Hodgkin's lymphomas contained HECA-452 positive high endothelial venules. These observations suggest that the HECA-452 antigen might be related to a skin-associated type of lymphoid tissue and to lymphomas originating in the skin. However, the results of HECA-452 expression in secondary sites, and the clinical data of the primary cutaneous large cell lymphomas did not support the concept that HECA-452 is functionally involved in homing to the skin, or that loss of the HECA-452 antigen is related to tumour progression of primary cutaneous T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of CD28CD4 T cells in living kidney transplant patients with long-term allograft acceptance

CD28⁻CD4⁺ T-cell subpopulation is expanded in kidney allograft patients with long graft survival. To seek for the roles of CD28⁻CD4⁺ T cells in the long-term acceptance of kidney allografts, we characterized this population by analyzing cell surface molecules, TCR V_β repertoire, mixed lymphocyte reaction (MLR), and cytokine production. The number of CD28⁻CD4⁺ T cells increased correlatively with time after transplantation in this group of patients. The CD28⁻CD4⁺ T cells did not express detectable levels of CD25, CD69, V24, or CTLA-4 but expressed heterogeneous amounts of CD45 RA on the surface. Freshly sorted CD28⁻CD4⁺ T cells revealed a restricted V_β repertoire, whereas the V_β usage of CD28⁺CD4⁺ T cells from the same patients was much diversified. Expression levels of TGF-β and IFNγ gene were significantly higher in the CD28⁻ CD4⁺ T cells than in the CD28⁺CD4⁺ T cells from the kidney allograft patients. These findings suggest that an oligoclonal CD28⁻ CD4⁺ T-cell population is continuously activated in patients with long allograft survival, which may be linked with the long-term acceptance.     

Identical expression of ELAM-1, VCAM-1, and ICAM-1 in sarcoidosis and usual interstitial pneumonitis

Extravasation of leucocytes in tissues is mediated by leucocyte—endothelial cell interactions in which adhesion molecules play an important role. Until now, two pathways have been unravelled, i.e., the LFA-1/ICAM-1 and the VLA-4/VCAM-1 pathways. ELAM-1 has been shown to be involved in granulocyte accumulation and recently also in lymphocyte migration. The role of HECA-452 is under investigation. In this study we have investigated the expression of the above-mentioned adhesion molecules in lung tissue of patients with pulmonary sarcoidosis and usual interstitial pneumonitis (UIP), and in mediastinal lymph nodes of patients with sarcoidosis. ICAM-1 (CD54) was broadly distributed on the endothelium of all the vessels found in sarcoidosis and UIP. VCAM-1 was present on the endothelium of the venules, capillaries, and arterioles in both sarcoidosis and UIP. ELAM-1 reacted with endothelial cells lining venules and capillaries in chronic progressive sarcoidosis and in the active phase of UIP but not in the stationary phases of both diseases. HECA-452 activity could be detected only on high endothelial venules within sarcoid lymph nodes. In lung tissues, macrophages bearing the ICAM-1 antigen were present in sarcoid tissue but not in the interstitium and alveolar space of UIP. LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) were present on all leucocytes found but seemed to be more highly expressed on lymphocytes in sarcoidosis. These findings suggest that the LFA-1/ICAM-1 and VLA-4/VCAM-1 pathways are involved in leucocyte migration in both types of lung disease, while in the active phases of sarcoidosis and UIP, ELAM-1 is also involved.     

A study of CD45RO, CD45RA and CD29 antigen expression on human decidual T cells in an early stage of pregnancy

The decidua is the place where the fertilized egg is implanted and where the immunocompetent cells of the mother come into direct contact with genetically disparate cells of the conceptus. Although the T cells in the decidua are exposed to fetal antigens, the fetus is not rejected by maternal immunocompetent cells. In the present study, we examined surface markers to determine whether the T cells in the human decidua are naive T cells without or memory T cells with a history of antigen stimulation. Although few T cells were present in the decidua, as compared to the peripheral blood, CD45RO⁺, CD29⁺ and CD45RA⁻ CD4⁺ T cells as well as CD45RO⁻, CD29⁺ and CD45RA⁻ CD8⁺ T cells, which are considered to be memory T cells, were in the majority, with only small numbers of CD45RO⁻, CD29⁻ and CD45RA⁺ CD4⁺ and CD8⁺ cells, which are naive T cells, present. Also, the decidual mononuclear cells secreted IL-2 and IL-4. Since IL-4 is secreted only by memory T cells, it is suggested that in the decidua memory T cells increase in number and secrete cytokines, thereby in some way influencing the phenomenon of fertility.     

Impairment of B and T cell maturation in gut associated lymphoid tissues due to malnutrition during lactation

Previously we found that malnutrition during lactation in rats produces an impairment in the immune response to cholera toxin. In this report we found that malnutrition during lactation provokes in 28-day-old rats an increase of Thy1⁺ cμ⁺ cells in gut associated lymphoid tissues concomitantly with a decrease of sIgA⁺ B cells. No differences were found in the percentages of the IgM⁺B cell populations. Furthermore, no differences were found in the Peyer's patch (PP) and mesenteric lymph node (MLN) T cell subsets in weaning rats when compared to controls. However, after 1 week of refeeding a higher percentage of the Thy1⁺ cμ⁻ subset together with a lower percentage of CD5⁺, CD4⁺, and CD8⁺ T cells, were found in malnourished rats when compared to controls. The above results may indicate that B-cell maturation is delayed in malnourished rats at two stages of differentiation: (a) in the passage of pre-B cells (Thy1⁺ cμ⁺) to immature B cells (sμ⁺), and (b) in the switch from sμ⁺ B cells to s⁺ B cells. The decrease of CD5⁺, CD4⁺, and CD8⁺T cells together with and increase of the Thy1⁺ cμ⁻ subset in gutassociated lymphoid tissues (GALT) may indicate that T-cell maturation is also delayed. Results obtained at weaning may be due to an engraftment by maternal milk-derived lymphocytes in the pups.     

Cell mediated immunity changes in ageing, relative importance of cell subpopulation switches and of nutritional factors

Decreased T-cell functions with ageing have been extensively described. This review focuses on recent data on changes in T-cell subpopulations related to ageing and their consequences on T-cell proliferation. Increase of immature T cells CD2⁺ CD3⁻ is an ageing phenomenon related to T-cell declining proliferation. Recently it was shown that increase of immature T cells was due to an increase in different subtypes of the CD2⁺ CD3⁻ population, double-negative CD2⁺ CD4⁻ CD8⁻ and double-positive CD2⁺ CD4⁺ CD8⁺ subpopulations, the former being associated with nutritional deficit, the latter with associated diseases. Other authors have focused on decreases of naive T cells with parallel increase of memory T cells; such a switch is also relevant to declining T-cell proliferation. This review focuses on two major factors which influence immune ageing: nutritional parameters and antigen exposure.     

Human suppressor T cells: Induction, differentiation, and regulatory functions

T-cell-mediated suppression of human immune responses involves a complex interaction between distinct lymphocyte subsets with suppressor-inducer and suppressor-effector functions. Recent studies with subset-specific monoclonal antibodies have defined a characteristic phenotype of suppressor-inducer cells (CD4⁺ Leu8⁺ 2H4⁺ 4B4⁻) that can be distinguished from that of helper cells for antibody synthesis (CD4⁺ Leu8⁻ 2H4⁻ 4B4⁺). Similarly, suppressor-effector cells (CD8⁺ CD11⁺ Tp44⁻ can typically be defined as a subset separable from cytotoxic T cells (CD8⁺ CD11⁻ Tp44⁺). Both antigen-specific and nonspecific interactions are important in suppressor T-cell activation and function. Soluble signals required for differentiation of CD8⁺ suppressor cells include an indomethacin-sensitive monocyte product and interferon gamma. In contrast, proliferation of the CD8⁺ suppressor cell subset depends on stimulations first by a product of CD4⁺ Leu8⁺ cells, T suppressor cell growth factor, and second by interleukin 2. Although the molecular basis of antigen-specific interactions between CD4⁺ and CD8⁺ cells in suppressor cell generation has not been defined, it may involve both conventional, presumably MHC-restricted, interactions between antigen and antigen receptors, as well as anti-idiotypic interactions of suppressor-effectors with determinants on suppressor-inducer receptors. Progress in elucidating requirements for activation, growth, and differentiation of suppressor cells should facilitate long-term culture of such cells and lead to clearer understanding of mechanism of suppressor-cell mediated immunoregulation.     

In the absence of Ii, MHC class II molecules display a distinct set of self peptides

The influence of the invariant (Ii) chain on antigen presentation by MHC class II molecules is well established. This study addresses whether the absence of Ii leads merely to failure of presentation of certain peptides or to display of novel peptides from endogenous proteins, using transfectants expressing HLA-DR alone, DR + Ii, or DR + Ii + DM. Western blotting revealed that, in the absence of Ii and DM, DR molecules form complexes with multiple intracellular proteins, furthermore, HPLC traces of peptides acid extracted from DR molecules expressed with or without Ii were markedly different. T cells were then used as “probes” of peptide occupancy of DR1. Most anti-DR1 alloreactive T cell clones raised against DR1 PBMC did not recognise DR1 in the absence of Ii and DM. Responses of clones that recognized the DR1⁺Ii⁻DM⁻ transfectants were augmented by co-expression of Ii and DM. In contrast, anti-DR1 clones generated against the DR1⁺Ii⁻DM⁻ transfectants failed to respond to human DR1-B-LCL. Responses to the DR1⁺Ii⁻DM⁻ transfectants were abolished by co-expression of Ii and DM in the transfected cell line, excluding simple lineage-specific allorecognition. These results suggest that, in the absence of Ii, class II molecules display a distinct set of peptides, generated as a result of interactions with proteins early in the biosynthetic pathway. If circumstances arise in vivo when the ratio of Ii to MHC class II is reduced, this may lead to the display of “illegitimate” self peptides, and the consequent interruption of self tolerance.     

A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites.

It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CD8+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-delta-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion molecule high, CD45R low putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA-452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5% of lymphocytes within the T-cell areas of these tissues expressed this antigen, whereas in inflammatory skin lesions (n = 16), 85% were HECA-452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among lymphocytes, the preferential expression of the HECA-452 determinant by cutaneous T cells supports the hypothesis that the skin constitutes a immunologically unique lymphoid tissue and suggests that this molecule may play a role in either lymphocyte homing to skin or in lymphocyte interactions with the epidermis.     

Functional evidence that the HECA-452 antigen is involved in the adhesion of human neutrophils and lymphocytes to tumour necrosis factor-alpha-stimulated endothelial cells.

The migration of leucocytes into tissues is a process mediated by leucocyte endothelial interactions, in which adhesion receptors play a crucial role. Recently, it was found that 80-90% of T cells in inflammatory skin diseases were reactive to the monoclonal antibody (mAb) HECA-452+ in contrast to inflamed non-cutaneous tissues. It was suggested that the HECA-452 antigen is a homing receptor for lymphocyte migration into skin. This receptor was designated cutaneous lymphocyte-associated antigen or CLA and subsequently identified as a group of related sugar moieties. E-selectin, formerly known as ELAM-1 expressed by the endothelium has been implicated to be a counter-receptor for CLA. In this study, we investigated the adhesion of HECA-452+ leucocytes, i.e. freshly isolated neutrophils and B-cell line BV173 to tumour necrosis factor-alpha (TNF-alpha)-stimulated (E-selectin+) endothelial cells. We found that the adhesion of these cells could be inhibited significantly by mAb HECA-452, in a similar fashion to CSLEX1, a mAb specific for E-selectin ligand sialyl Lewisx. This inhibiting effect of both mAb on the adhesion of polymorphonuclear leucocytes (PMN) and BV173 could only be demonstrated when the assay was performed at 4 degrees, but not at 37 degrees. Furthermore, using immunohistochemical analysis we found that the mAb HECA-452-reactive epitope is different from that recognized by CSLEX1. The present results give direct evidence that the antigen recognized by HECA-452 is involved in the adhesion of leucocytes to endothelial cells, although this antigenic epitope is different from that reactive to CSLEX1.     

Aberrant expression of CD56 by circulating Sézary syndrome malignant T lymphocytes

Sézary syndrome (SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically displays a CD3⁺ CD4⁺ CD45RO⁺ memory T cell phenotype. We report a case of SS with an aberrant CD56⁺ immunophenotype. This patient presented with a generalized erythroderma and palpable small axillary lymph nodes. SS (stage IVA) was diagnosed on histological criteria and by the detection of a major T cell clone in skin and blood, an elevated CD4/CD8 T cell ratio and Sézary cells count > 1000/mm³. Beside the Sézary cell marker KIR3DL2, immunostainings revealed that two third of the malignant cells expressed CD56 but no other natural killer (NK) cell marker such as CD16, CD160 or NKp46. This atypical expression was not linked to an activation-dependent process and remained stable during the time course of the disease. No loss of the pan T-cell markers CD2, CD3 or CD4 was detected while a complete down-modulation of CD26 was observed. Despite several lines of treatment, no durable amelioration was observed and patient died after 10 mo of follow-up. Because this CD4⁺ CD56⁺ SS case is the only one reported so far, the functional significance of CD56 expression remained difficult to assess in terms of aggressiveness and prognosis.     

CD3+、CD4+和CD8+ T细胞Vβ亚家族中PD-1免疫表型检测方法的建立

 目的：建立分析CD3⁺、CD4⁺和CD8⁺ T细胞Vβ亚家族中免疫抑制性受体程序性细胞死亡蛋白1（PD-1）分子免疫表型的方法,从而了解人体外周血T细胞谱系中PD-1表型细胞的分布频率。方法：收集健康个体（HI）外周血10例,利用抗CD45、CD3、CD4、CD8、PD-1等多色荧光流式单抗,以及T细胞受体（TCR）Vβ谱系试剂盒[IOTest^® Beta Mark TCR Vβ Repertoire Kit,共8管,每一管均为FITC和PE偶联的复合抗体（A~H）,每一管复合抗体包含3个TCR Vβ亚家族的抗体],检测T细胞亚群TCR Vβ亚家族中PD-1的分布情况。结果：在10例HI的检测中,CD3⁺、CD3⁺CD4⁺和CD3⁺CD8⁺ T细胞亚群中检测的24个TCR Vβ亚家族总和符合试剂盒所提供的Quick Reference Card数据,初步结果显示,HI中CD3⁺ T细胞主要优势TCR谱系是Vβ2、Vβ3、Vβ8、Vβ9、Vβ5.1、Vβ13.1和Vβ13.2;而在CD3⁺CD4⁺ T细胞中的优势利用主要集中在Vβ2、Vβ3、Vβ8、Vβ9、Vβ5.1和Vβ13.1;在CD3⁺CD8⁺ T细胞中则主要为Vβ1、Vβ2、Vβ3、Vβ9、Vβ13.1和Vβ13.2等亚家族。进一步分析显示PD-1⁺细胞在HI的CD3⁺、CD3⁺CD4⁺和CD3⁺CD8⁺ T细胞24个TCR Vβ亚家族中均可以检测到,PD-1⁺细胞在T细胞各亚群中分布频率有个体差异,在CD4⁺ T细胞中,以Vβ5.2⁺ T细胞的分布频率较高,而在CD8⁺ T细胞中,以Vβ11⁺和Vβ13.6⁺ T细胞的分布频率较高。结论：本项工作利用健康人样本成功建立了多色荧光流式细胞术检测T细胞亚群TCR Vβ谱系中免疫抑制性受体PD-1分子免疫表型的方法,为进一步应用于分析白血病等病人TCR Vβ谱系的免疫抑制特点提供了新方法。     

Analysis of Responsive Cells in Tolerance by the Oral Administration of Ovalbumin

The induction of immune tolerance is the most common consequence of protein feeding, i.e., “oral tolerance”. In this study we investigated the genetic basis of oral tolerance using various kinds of recombinant and congenic mice, and the cells involved in the development of this phenomenon in mice. The footpad swelling response to ovalbumin (OVA) was inhibited in mice that were orally fed OVA 7 days before sensitization. No effect of strain of mouse was seen in this inhibition. This inhibition could be transferred by Peyer's patch cells. The CD4^-8⁺ T cells were responsible for the inhibition of footpad swelling. The number of CD4⁺ cells from OVA-fed tolerant mice decreased significantly, but CD8⁺ cells did not.

The number of CD4^-8⁺ T cells was increased in Peyer's patches of OVA-fed tolerant mice, and were involved in the development of oral tolerance.     

Activation status of T and NK cells in the endometrium throughout menstrual cycle and normal and abnormal early pregnancy

Endometrial lymphocytes were studied at all stages throughout the menstrual cycle and early pregnancy by flow cytometry to examine different lymphocyte subpopulations and the expression of the T- and NK-cell activation markers. After pregnancy, CD8⁺CD3⁺ lymphocytes were decreased in the decidua. In both endometrium and decidua, more T cells expressed CD69, CD71, HLA-DR, and CD38 antigens than in peripheral blood. After pregnancy, CD71⁺CD3⁺ lymphocytes were further increased. CD25⁺CD3⁺ lymphocytes decreased significantly in the endometrium and decidua of ectopic pregnancies, but not in the decidua of normal pregnancies. These findings indicate that T cells are regionally activated in the first trimester, and it may be the result of the stimulation by fetal antigens. NK cells were the most abundant cell type in the decidua, which expressed the phenotype CD16⁻ CD56⁺, and CD57⁻CD56⁺. The proportion of activated decidual NK cells was increased in anembryonic pregnancies more than in normal pregnancies, although the total NK subpopulation was similar in both groups. This might result in increased NK cytotoxicity in anembryonic pregnancies. In conclusion, T cells are activated, but NK cytotoxicity is decreased in the decidua of early normal pregnancies. This might be important in the control of trophoblast growth and placental development.     

CD8+ T Cell Subsets in Aging

Infections are a major cause of illness and death amongst elderly people. Peripheral blood CD8⁺ T lymphocytes -which play a crucial role in host defence against viral infections-, are divided in subsets based upon the expression of several cell and activation markers. Since in senescence changes in peripheral blood CD8⁺ T lymphocyte compartment have been described, studies were performed to determine whether in aging there are variations in the peripheral blood CD8⁺CD38⁺, CD8⁺CD57⁺, CD8⁺HLA-DR⁺, CD8⁺CD45RA⁺ and CD8⁺CD45RO⁺ cell subset. A decrease in the CD8⁺CD45RA⁺ lymphocytes was observed, indicating that variations in the CD8⁺ compartment can take place with ageing.