The role of gamma/delta T cells in progesterone-mediated immunomodulation during pregnancy: a review.

PROBLEM: To determine if pregnancy is recognized by the immune system and if inadequate recognition of fetal antigens might result in failed pregnancy. METHOD OF STUDY: Review of literature and current data. RESULTS: In the decidua gamma/delta TCR positive cells significantly increase in number. A subset of gamma/delta T cells reacts with nonpolymorphic Class I or Class I like molecules. Trophoblast recognition is mediated by the V gamma 1 subset which recognize a conserved mammalian sequence on the trophoblast. Almost all gamma/delta T cells in the decidua are activated and use the V delta 1 chain, whereas the majority of human peripheral gamma/delta lymphocytes expresses V gamma 9/V delta 2 TCR. Peripheral gamma/delta T cells of healthy pregnant women preferentially use V gamma V delta 1 chains, on the other hand, those of recurrent aborters use the V gamma 9V delta 2 combination. Signaling via the V gamma 1.4V delta 1 receptor induces a Th2 type response, whereas activation of the lymphocytes via the V gamma 9V delta 2 receptor results in increased IL-12 production and natural killer (NK) activity. In the presence of progesterone, activated lymphocytes synthesize the progesterone induced blocking factor (PIBF), which inhibits NK activity and exerts an anti abortive effect in vivo. Decidual CD56+ and gamma delta+ cells are to a high extent the same population. CONCLUSION: All decidual CD56+ cells express PIBF, thus it cannot be excluded that local production of this substance contributes to low decidual NK activity and thus to the success of the pregnancy.     

Expression profiles of peripheral CD160+ lymphocytes during the course of healthy human pregnancy

Citation
Barakonyi A, Weisdorn R, Miko E, Varga P, Bodis J, Szekeres‐Bartho J, Szereday L. Expression profiles of peripheral CD160⁺ lymphocytes during the course of healthy human pregnancy. Am J Reprod Immunol 2011; 66: 137–142 Problem CD160 receptor is expressed by natural killer (NK) and T‐cell subsets, and after activation, it could enhance cytotoxicity or pro‐inflammatory cytokine production on NK cells. Here, we investigated the phenotype of peripheral CD160⁺ cells during healthy pregnancy. Method of study We analyzed the expression of CD69 activation marker, gamma/delta TCR, and NKG2A or NKG2D NK cell receptors on CD160⁺ lymphocytes of non‐pregnant and healthy pregnant women at four different stages of pregnancy by flow cytometry. Results In our hands, CD160 receptor‐positive lymphocytes were present during pregnancy; however, they had different characteristics depending on gestational age. During implantation, CD160⁺ cells showed low activation rate, decreased NK receptor expression while 40% of Vδ2 + T cells expressed CD160 receptor. In turn, all the above parameters increased as pregnancy proceeds. Conclusion Our results indicate that CD160⁺ lymphocytes could be able to play a role in the maintenance of healthy pregnancy.     

The role of gamma/delta T cell receptor positive cells in pregnancy.

PROBLEM: Due to the lack of classical HLA antigens on the trophoblast, fetal antigens are possibly presented in a non major histocompatibility complex (MHC) restricted way. Decidual gammadelta T cells, which significantly increase in number during pregnancy, might play a role in recognition of fetal antigens and also in determining the quality of the response to these antigens. Our study was aimed at investigating the role of this cell population in progesterone-dependent immunomodulation. METHOD OF STUDY: Peripheral lymphocytes from healthy pregnant women and from habitual aborters were tested by immunocytochemistry for the presence of gamma/delta T cell receptor (TCR) and progesterone receptor. To investigate the effect of treatment with a pan anti gamma/delta antibody, lymphocytes were incubated for 3 hr with the antibody, and then interleukin (IL)-10, IL-12 and progesterone-induced blocking factor (PIBF) expression (by immuno-cytochemistry) as well as natural killer (NK) cell activity were determined. RESULTS: In peripheral blood of healthy pregnant women the percentage of gamma/delta TCR+ cells was significantly higher (P < 0.001) than in that of recurrent aborters or of non-pregnant individuals. Ninety-seven percent of gamma/delta TCR+ pregnancy lymphocytes expressed progesterone receptor. Binding of a specific antibody to the gamma/delta TCR inhibited PIBF- as well as IL-10 production, whereas it increased NK activity and IL-12 expression. CONCLUSIONS: These data suggest the role of gamma/delta TCR-bearing lymphocytes in progesterone-dependent immunomodulation.     

The role of gamma/delta T-cell receptor-positive cells in pregnancy: part II.

PROBLEM: We have previously demonstrated a significantly increased ratio of gamma/delta T-cell receptor (TCR)-positive progesterone receptor(PR)-positive cells in the peripheral blood of healthy pregnant women compared to that of recurrent aborters or non-pregnant individuals. Treatment of pregnancy lymphocytes with a pan anti-gamma/delta TCR antibody inhibits progesterone-induced blocking factor (PIBF) production, increases natural killer (NK) activity, and alters the cytokine profile. The present study was aimed at investigating the role of the different gamma/delta subpopulations in these phenomena. METHOD OF STUDY: Peripheral blood lymphocytes from healthy pregnant women were incubated with either anti-gamma1.4 and delta1, or anti-gamma9 and delta2 antibodies. The effect of these treatments on PR induction and interleukin (IL)-10 and IL-12 expression were tested by immunocytochemistry. NK activity of anti-gamma/delta treated lymphocytes was also determined. RESULTS: In peripheral blood of healthy pregnant women, the most frequently occurring chain combination was gamma1.4/delta1, whereas in recurrent aborters, the gamma9/delta2 combination was predominant. Treatment of normal pregnancy lymphocytes with a mixture of gamma1.4 and delta1 antibodies resulted in a significantly reduced NK activity and increased PR and IL-10 expression, whereas treatment with a mixture of gamma9 and delta2 antibodies significantly reduced IL-10 production and slightly increased IL-12 production and NK activity. These data suggest the presence of two functionally distinct subpopulations in the peripheral blood of pregnant women.     

V-chain preference of gamma/delta T-cell receptors in peripheral blood during term labor

PROBLEM: An altered function of the maternal immune system creates a favorable environment for the developing fetus during pregnancy. At term, new regulatory mechanisms are activated, to initiate labor. Earlier we showed that in peripheral blood of pregnant women gamma/delta T cells of cytotoxic phenotype are replaced by those of a non-cytotoxic phenotype. Here we studied the Vgamma and Vdelta chain usage of peripheral gamma/delta T cells from women in labor. METHOD OF STUDY: Vgamma and Vdelta chain expression on peripheral blood lymphocytes obtained at the 3rd trimester of pregnancy and during parturition were examined by immuncytochemistry and flow cytometry. RESULTS: Increased % of Vgamma9/Vdelta2 and decreased % of Vgamma4/Vdelta1 T cells were found in peripheral blood during labor, together with unaltered percentages of single Vgamma+ or Vdelta+ cells. The initially high Vgamma4/Vdelta1 to Vgamma9/Vdelta2 ratio decreased during labor. CONCLUSION: The initiation of labor is characterized by an altered V-chain usage of gamma/delta T cells.     

Double-edged effect of Vgamma9/Vdelta2 T lymphocytes on viral expression in an in vitro model of HIV-1/mycobacteria co-infection

A reciprocal influence exists between mycobacteria and HIV: HIV-infected individuals are more susceptible to mycobacterial infections and, on the other hand, mycobacterial infection results inacceleration of HIV disease progression. Vgamma9/Vdelta2 T lymphocytes are known to participate in the defense against intracellular pathogens, including Mycobacterium tuberculosis. Indeed, they kill mycobacteria-infected macrophages and, upon recognition of mycobacterial Ag, release TNF-alpha and IFN-gamma, which are also up-regulators of HIV expression. To assess whether mycobacteria-activated gamma delta T lymphocytes contribute to the enhancement of HIV replication, we established an in vitro model mimicking HIV and mycobacteria co-infection with the latently HIV-infected promonocytic U1 cell line and Vgamma9/Vdelta2 peripheral lymphocytes stimulated with mycobacterial Ag. gamma delta T cell activation determined two distinct, but connected effects, namely U1cell death and HIV expression. Both effects were mainly mediated by release of TNF-alpha and IFN-gamma from activated gamma delta lymphocytes, although Fas-FasL interaction also contributed to U1 apoptosis. The final outcome on U1 survival, and thus, on HIV expression, highly depended on mycobacterial Ag concentration coupled to the differential secretory potency of gamma delta cells. In particular, the induction of viral expression prevailed at low Ag concentration and with lower cytokine production by mycobacteria-activated gamma delta cells. Notably, during the course of HIV infection, Vgamma9/Vdelta2 lymphocytes are reported to be functionally impaired and may thus indirectly influence the progression of HIV disease. In addition, a predominant inhibition of viral replication was encountered when mycobacteria-activated gamma delta T cells were co-cultured with primary HIV-infected macrophages. Thus, we suggest that specific recognition of mycobacterial Ag by gamma delta T lymphocytes in co-infected individuals may modulate viral replication through the complex array of soluble factors released.     

Preferential activation of peripheral blood V gamma 9+ gamma/delta T cells by group A, B and C but not group D or F streptococci.

Previous studies have established that inactivated mycobacteria are potent and selective activators of V gamma 9+/V delta 2+ human gamma/delta T cells. Here we have analysed the proliferative response of human gamma/delta T cells to five serologically distinct groups of streptococci. While heat-inactivated streptococci of all five serogroups tested (A, B, C, D and F) induced a strong proliferative response in peripheral blood mononuclear cells (PBMC), only groups A, B and C elicited a selective activation of V gamma 9+ gamma/delta T cells in 10 (serogroup B) or 11 (serogroups A and C) of 11 tested healthy individuals. In striking contrast, groups D and F streptococci failed to activate gamma/delta T cells in nine of 11 donors and induced only a weak gamma/delta T cell response in two additional individuals. Depletion of V gamma 9+ T cells before culture completely eliminated all gamma/delta T cell responses to streptococci. These data indicate that groups A, B and C (but not D or F) streptococci can be included in the growing list of selective ligands for V gamma 9+/V delta 2+ human gamma/delta T cells.     

Gamma/delta T cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy

Earlier data suggest that gamma/delta T cells may play an important role in the immune response to Mycobacterium tuberculosis. The aim of this study was to determine the percentage of different gamma/delta subsets in peripheral blood of active tuberculosis patients with a positive or negative tuberculin reaction. Thirty-eight patients infected with M. tuberculosis and 22 healthy controls were included in the study. Venous blood was taken before starting antimycobacterial treatment. Lymphocytes were reacted with monoclonal antibodies specific for different gamma/delta V chains (Vdelta1, Vdelta2, Vgamma9 and Vgamma4). The results were analysed in the context of tuberculin reactivity and X-ray findings. Our results revealed a selective loss of Vgamma9/Vdelta2 T cells in the peripheral blood of tuberculin-negative patients with active tuberculosis compared to healthy controls, while the ratio of Vgamma9/Vdelta2 T cells in the peripheral blood of patients with a positive skin test did not differ from that of healthy controls. These findings demonstrate a relationship between the loss of the major M. tuberculosis-reactive subset of gammadelta T cells and the absence of tuberculin reactivity. The data are consistent with the hypothesis that gammadelta T cells play a role in the protective immune response to M. tuberculosis infection.     

Circulating gamma/delta T lymphocytes from systemic sclerosis (SSc) patients display a T helper (Th) 1 polarization

Systemic sclerosis (SSc) is a connective tissue disease in which immune system activation is evidenced by high levels of different cytokines in the sera and/or in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by the presence of specific autoantibodies. gamma/delta T cells accumulate in the lung and the skin of SSc patients suggesting their potential role in the development and maintenance of the disease. The aim of this study was to assess cytokine production and cytotoxic activity of circulating gamma/delta T lymphocytes obtained from SSc patients and to evaluate their potential role during this disorder. Our results showed that both the proportion and the absolute number of IFN-gamma gamma/delta-producing cells (i.e. displaying a Th1 polarization) in SSc was significantly higher than either the proportion and the absolute number of IL-4 gamma/delta-producing cells in SSc or the proportion and the absolute number of IFN-gamma gamma/delta-producing cells in healthy controls (P < 0.05 for both groups). Furthermore, the cytotoxic activity of enriched gamma/delta T cells was significantly increased in SSc patients compared with controls. The results concerning the Vdelta1+ T cell subset paralleled those of total gamma/delta T lymphocytes. In contrast, alpha/beta T cells from SSc and control subjects displayed Th2 cytokine production. All these findings were independent of both disease subset and clinical status. Our data demonstrate that, although SSc is generally considered a Th2 autoimmune disease, Th1 polarization of gamma/delta T cells and an increase in their cytotoxic activity is observed in SSc, suggesting that gamma/delta T cells could have a relatively autonomous role in the pathogenesis in this disease.     

Human T cells in hu-PBL-SCID mice proliferate in response to Daudi lymphoma and confer anti-tumour immunity.

In vitro culture of human peripheral blood lymphocytes (PBL) with Daudi (Burkitt lymphoma) cells results in selective proliferation of V gamma 9/V delta 2 T cells with high cytotoxicity against Daudi cells. After adoptive transfer into severe combined immunodeficient (SCID) mice, these cells exert specific anti-tumour activity against Daudi lymphoma. To test whether cytotoxic V gamma 9/V delta 2 T cells are induced in SCID mice, human PBL injected intraperitoneally were stimulated with irradiated Daudi cells (PBL/Daudi-SCID). After 7-14 days, PBL/Daudi-SCID had a significantly higher percentage of human gamma delta T cells in their peritoneal cavity, lymph nodes and blood than controls (PBL-SCID). DNA content analysis of T cell subsets from PBL/Daudi-SCID showed a significantly higher percentage of cells in S + G2 + M phases of the cell cycle in the TCR-gamma delta-1+ than in CD3+ cell population. Human cells recovered from PBL/Daudi-SCID showed specific cytotoxicity against Daudi cells. PBL/Daudi-SCID inoculated with a lethal dose of Daudi lymphoma survived significantly longer than controls. This protection was specific for Daudi cells and was not mediated by murine natural killer (NK) cells. Thus human peripheral blood T cells grafted in SCID mice proliferate in response to antigen and confer specific immunity.     

Reduction in T gamma delta cell numbers and alteration in subset distribution in systemic lupus erythematosus.

We have studied the distribution of T gamma delta cells in the peripheral blood of 35 patients with systemic lupus erythematosus (SLE) and 36 age-matched controls. The monoclonal antibodies A13, BB3 and Ti gamma A, which are specific for the V delta 1, V delta 2 and V delta 9 gene products respectively, were used to define T gamma delta cell subsets. A significantly lower frequency of T gamma delta cells was found in peripheral blood lymphocytes of SLE patients compared with normal subjects (3.2% versus 5.9%). There was a marked reduction in the V delta 2+ subset of T gamma delta cells, which resulted in a reversal of the ratio of V delta 2+/V delta 1+ cells from 4.34 to 0.56. No correlation was found with either clinical or laboratory measures of disease activity. These results suggest that the observed changed in T gamma delta subset distribution are related to the SLE itself, and not secondary to changes in disease activity.     

The role of gamma/delta T cells in the feto-maternal relationship.

Polymorphic MHC is absent from the trophoblast, therefore, it resists NK as well as CTL-mediated lysis in vitro. Activated gamma / delta TCR positive cells are significantly enriched in the decidua as well as in peripheral blood of healthy pregnant women. Human peripheral gamma / delta lymphocytes preferentially express the V gamma 9/V delta 2 TCR, whereas those of the decidua use the V delta 1 chain. These subpopulations are functionally polarized, the former being Th1, the latter Th2. Potentially cytotoxic V delta 2+ lymphocytes recognize HLA-E on the trophoblast via the CD94/NKG2A receptor, which induces an inhibitory signal, thus potentially inhibiting Th1 type cytokine production.     

Human TcR gamma delta+ lymphocyte response on primary exposure to Plasmodium falciparum.

In 29 patients experiencing their first P. falciparum malarial attack, blood levels of TcR gamma delta+ lymphocytes were studied from the onset of infection to up to 6-9 months later. Blood TcR gamma delta+ lymphocytes, revealed using the TcR delta 1 monoclonal antibody (MoAb), were increased both in absolute and relative numbers. Alterations lasted for up to 3-4 months following the attack. A Ti gamma A/BB3 reactive V gamma 9 subset was preferentially amplified. In vitro, TcR gamma delta+ lymphocytes from both malaria-sensitized and unprimed donors responded to P. falciparum schizont extract (PFSE). PFSE-stimulated polyclonal T cell lines consisted principally in TcR gamma delta+ cells with a Ti gamma A+/BB3+ phenotype. Several TcR gamma delta+ T cell clones obtained from patients recovering from acute malarial attack were maintained in the presence of PFSE and autologous irradiated PBL. They belong to the V gamma 9 subset. In long-term cultures, TcR gamma delta+ clones progressively lost their capacity to react to PFSE antigen while they were able to proliferate and to exert cytotoxic activity in response to autologous TcR alpha beta+, PFSE-specific T lymphocyte clones. This suggests that regulatory interactions occur between activated TcR gamma delta+ and TcR alpha beta+ cells generated by P. falciparum. Sequential variations in blood TcR gamma delta+ and TcR alpha beta+ lymphocyte levels after primary exposure to P. falciparum suggest that such regulatory interactions may occur in vivo.     

Characterization of normal human CD3+ CD5- and gamma delta T cell receptor positive T lymphocytes.

The functional and phenotypic properties of normal human CD3+CD5- T cells which have a higher frequency of cytotoxic cells than CD3+CD5+ T lymphocytes have been described. Using three- and four-colour immunofluorescence flow cytometric cell sorting, the CD3+CD5- and CD3+CD5+ populations were subdivided into alpha beta or gamma delta T cell receptor positive cells. The four subsets were examined for the in vitro cytotoxic activity and were also stimulated with mitogens in limiting-dilution assays to measure the frequencies of proliferating and interleukin-2 (IL-2) producing cells. CD3+CD5- alpha beta +, CD3+CD5- gamma delta + and CD3+CD5+ gamma delta + cells had lower frequencies of proliferating and IL-2-producing cells than did CD3+CD5+ alpha beta + cells. However, the cytotoxic activity of the different phenotypes was higher in the CD3+CD5- subsets, especially when these cells were gamma delta +. Expression of gamma delta or lack of expression of CD5 appeared to be associated with the acquisition of cytolytic potentials. CD8 was expressed on 20% of fresh CD3+ gamma delta + cells. Cultured gamma delta + cells retained the expression of gamma delta, but quickly lost that of CD8 and with time modulated the expression of CD5. The expression of CD5 was found to be higher on sorted CD3+CD5+ gamma delta - than on CD3+CD5+ gamma delta + cells. These observations indicate that gamma delta is preferentially expressed on CD5-negative or weakly positive T lymphocytes and that CD3+CD5- gamma delta + cells appear to constitute a discrete small subset of mature T lymphocytes which are cytotoxic in nature. However, the exact immunological function of these cells and their place in T cell ontogeny are yet to be elucidated.     

Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating gamma delta+ T cells is correlated with disease activity.

The phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on gamma delta+ T cells and CD4-CD8- alpha beta+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages of CD4-CD8- alpha beta+ T cells in patients and controls; (ii) a significant decrease of the gamma delta+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating gamma delta+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/gamma delta+ T cells was significantly higher in patients with active disease. HLA-DR+/gamma delta+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated gamma delta+ T cells were predominantly V delta 1. Taken together, these data support the involvement of gamma delta+ T cells in the pathogenesis of RA.     

A subset of gamma delta lymphocytes is increased during HIV-1 infection.

The gamma delta T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the delta TCS1 monoclonal antibody, directed against the V delta 1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of gamma delta TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the delta TCS1+ (V delta 1+), CD8 +/- (dim staining) subset. Patients with high gamma delta TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpes viral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of gamma delta TcR T cells. Altogether these data show that the selective expansion of delta TCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system.     

Analysis of circulating gammadelta T cells in children affected by IgE-associated and non-IgE-associated allergic atopic eczema/dermatitis syndrome

Recent studies have suggested that not only alphabeta(+) T cells, but also the less common gammadelta(+) T cells may play a role as effectors and immunoregolatory cells in the development and perpetuation of allergic inflammation. The objective of this study was to focus on the role of gammadelta(+) T cells in atopic dermatitis (AD), a chronic relapsing inflammatory disease of the skin, often associated with allergic bronchial asthma. The present study employed flow cytometric analysis to compare numbers and phenotypic characteristics of gammadelta(+) T cells in the peripheral blood of children with atopic dermatitis and age-matched healthy controls. The percentage of circulating Vgamma 9Vdelta2(+) T lymphocytes was significantly increased in AD patients with respect to the age-matched controls, with a positive correlation with clinical score severity. The prevalent phenotype in both AD patients and controls was CD45RO(+), with no differences observed in the percentage of Vdelta2(+) CD45RO(+) between these groups. Conversely, memory CD45RO(+) CD62L(+) Vdelta2(+) lymphocytes were significantly lower in AD patients. Furthermore, naive circulating Vdelta2(+) T lymphocytes were significantly lower in AD children than in aged-matched controls. No correlation was observed between circulating Vgamma 9Vdelta2(+) expansion and IgE serum levels. It was concluded that an association exists between the levels of circulating gammadelta(+) T lymphocytes and atopic dermatitis, with a positive correlation with clinical score but no link with IgE serum levels. The pathophysiological role of gammadelta T lymphocytes in atopic dermatitis awaits further investigation.     

Skewed inhibitory receptors expression in a TAP2-deficient patient

Most of patients suffering from HLA class I deficiency due to mutations in TAP genes show a significative increase of the peripheral minor Vdelta1+ subpopulation of gammadelta T cells. Surface expression of inhibitory receptors (IR) for HLA class I molecules have been mainly attributed to Vdelta2+ gammadelta T clones. In this study we have analysed the expression of these receptors in both subsets of gammadelta T peripheral lymphocytes. We studied 16 healthy controls and a reported case of homozygous TAP2 mutation with a marked increase of Vdelta1+ gammadelta T cells. MICA/B presence in monocytes was also evaluated. In healthy subjects, the expression of CD94 and CD94/NKG2A was higher in the Vdelta2+ subset but cells bearing the IR ILT2 were found increased in the Vdelta1+. The patient Vdelta2+ gammadelta T cells showed the same IR expression than normal controls, in contrast the Vdelta1+ subset presented a special pattern of very high expression of CD94 and ILT2 and low of CD94/NKG2A. The presence of a new IR poorly represented in healthy individuals could account for the selective increase of Vdelta1+ gammadelta T in TAP-deficient patients. MICA/B surface expression in monocytes was not shifted in our patient.     

Increase of circulating gamma/delta T lymphocytes in the peripheral blood of patients affected by active inflammatory bowel disease.

In order to study the role of gamma/delta T cells in the pathogenesis of inflammatory bowel disease (IBD) in humans, we measured the percentage of these cells in the peripheral blood, assessed the ratio of the non-disulphide-linked (delta TCS1) type of T cell receptor (TCR) in the total gamma/delta T cells, studied the co-expression of gamma/delta TCR and accessory molecules CD8 and CD16, and compared these data with both the type and the activity of the disease. Percentage levels and absolute numbers of gamma/delta+ T cells were higher in active patients than in controls (P < 0.05), mainly as a result of an increase of V delta 1+ (delta TCS1) T cell subset (P < 0.05). This trend was strongly retained independently of disease activity and clinical picture. An increased percentage of TCR delta 1+/CD16+ cells was observed in our patients compared with controls (P < 0.05). In contrast, no difference was observed as far as the TCR delta 1+/CD8+ cells were concerned. These results suggest that IBD is associated with an expansion of gamma/delta T cells in peripheral blood, which may play a role in the pathogenesis of these disorders.