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At least 19 recordsLinked to original sources
PubMed1992

Immunohistochemical study of T cell receptor gamma delta cells in chronic liver disease.

The distribution and phenotypic characterization of T cell receptor (TCR) gamma delta cells in human liver tissue was investigated immunohistochemically at light and electron microscopic levels. In chronic liver disease, there was a significant increase in the number of TCR gamma delta cells and in the percentage of TCR gamma delta cells to CD3+ cells in the portal areas and hepatic sinusoids. Hepatic TCR gamma delta cells were classified as small or large gamma delta cells. Large gamma delta cells were increased in chronic liver disease, whereas both small and large gamma delta cells were increased in the portal areas and hepatic sinusoids in liver cirrhosis. The increased TCR gamma delta cells were of the BB3+ (peripheral) type, indicating that TCR gamma delta cells in the liver were of the same lineage as those in the peripheral blood. In addition, the majority of the TCR gamma delta cells in the portal areas of liver cirrhosis patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed that the large gamma delta cells were lymphoblastoid and contained multivesicles. The present study clearly demonstrated that there are two types of TCR gamma delta cells, and that these cells were significantly increased in the livers of patients with chronic liver disease. This suggests that they may be involved in regulation of the immune response and hepatocellular damage in chronic liver disease.

Adult↗
PubMed1993

Development of T cell receptor-gamma delta cells. Phenotypic and functional correlations of T cell receptor-gamma delta thymocyte maturation.

The development of TCR-gamma delta cells during thymic ontogeny has been studied using fetal thymic organ cultures of normal and transgenic (Tg) mice. The expression of the cell-surface markers--heat stable Ag (HSA), MEL-14, CD5, CD25 (IL-2R), and CD44 (Pgp-1)--correlated with TCR-gamma delta maturation. As the fetal thymus developed, there was an increase in HSA-, CD5dull, and CD44+ cells for each TCR-gamma delta cell subset. Moreover, the expression of recombination activating genes-1 and -2 (RAG-1 and RAG-2) also correlated with TCR-gamma delta maturation as only HSA+ TCR-gamma delta cells transcribed these genes. Cyclosporin A inhibited the development of the TCR-gamma delta thymocytes if it was introduced early during thymic ontogeny by arresting the differentiation of TCR-gamma delta thymocytes at the HSA+ stage. Immature HSA+ TCR-gamma delta thymocytes isolated from both TCR-gamma delta Tg and normal mice did not respond to nominal Ag or anti-TCR mAb unless exogenous IL-2 was added to the cultures. In contrast, HSA- TCR-gamma delta cells from Tg and normal mice responded to TCR/ligand interactions in the absence of additional IL-2. Finally, the development of functionally mature TCR-gamma delta cells could be induced in vitro. Interaction of the HSA+ Tg+ TCR-gamma delta cells with anti-TCR-gamma delta mAb or Ag-bearing thymic stromal cells resulted in RAG-1 and RAG-2 down-regulation. These data strongly suggest that TCR-gamma delta HSA+, RAG+ thymocytes differentiate into a more mature stage under the pressure of positive selection and that TCR-gamma delta cell development is regulated in a manner similar to TCR-alpha beta cells. In addition, the ability of Cyclosporin A to inhibit TCR-gamma delta cell development combined with the findings that Ag-bearing stromal cells can induce Tg TCR-gamma delta cell development suggests that maturation and selection of TCR-gamma delta cells depends on receptor-mediated physiologic stimuli delivered during thymic development.

Animals↗
PubMed1996

Selectively impaired development of intestinal T cell receptor gamma delta+ cells and liver CD4+ NK1+ T cell receptor alpha beta+ cells in T cell factor-1-deficient mice.

T cell factor-1 (Tcf-1) is a transcription factor that binds to a sequence motif present in several T cell-specific enhancer elements. In Tcf-1-deficient (Tcf-1-/-) mice, thymocyte development is partially blocked at the transition from the CD4-8+ immature single-positive stage to the CD4+8+ double-positive stage, resulting in a marked decrease of mature peripheral T cells in lymph node and spleen. We report here that the development of most intestinal TCR gamma delta+ cells and liver CD4+ NK1.1+TCR alpha beta+ (NK1+T) cells, which are believed to be of extrathymic origin, is selectively impaired in Tcf-1-/- mice. In contrast, thymic and thymus-derived (splenic) TCR gamma delta+ cells are present in normal numbers in Tcf-1-/- mice, as are other T cell subsets in intestine and liver. Collectively, our data suggest that Tcf-1 is differentially required for the development of some extrathymic T cell subsets, including intestinal TCR gamma delta+ cells and liver CD4+ NK1+T cells.

Animals↗
PubMed1990

T gamma delta cells in juvenile rheumatoid arthritis and rheumatoid arthritis. In the juvenile rheumatoid arthritis synovium the T gamma delta cells express activation antigens and are predominantly V delta 1+, and a significant proportion of these patients have elevated percentages of T gamma delta cells.

Using the anti-TcR gamma/delta-1 monoclonal antibody and flow cytometry, we examined the number of T gamma delta cells in paired samples of peripheral blood and synovial fluid or tissue from 24 children with juvenile rheumatoid arthritis (JRA), five adult patients with JRA, and 14 patients with rheumatoid arthritis (RA). No significant difference was found in the synovial compartment T gamma delta values compared with the blood in JRA, adult JRA, or RA patients. Nor was any significant difference found in the peripheral blood or synovial compartment T gamma delta values in any of the three patient groups compared with the peripheral blood of normal controls. However, seven of the children with JRA had very high T gamma delta values in the synovial compartment while none of the normal children had high T gamma delta values in the blood (P = 0.02, Fisher's exact test). This may indicate a possible separate JRA patient group with high T gamma delta levels in the synovial compartment. In six JRA patients further analysed for T gamma delta subpopulations, a significant predominance of V delta 1+ cells was found in the synovial compartment compared with the corresponding peripheral blood samples (P less than 0.05, Wilcoxon's signed test) and with peripheral blood of child controls (P less than 0.05, Mann-Whitney U test). In these six patients, the T gamma delta-cell expression of the very early activation antigen CD69 were significantly higher (P less than 0.05, Wilcoxon's signed test) in the synovial compartment compared with the peripheral blood. Synovial T gamma delta cells expressing HLA-DR and interleukin 2 receptors could also be detected, in contrast to the peripheral blood in which no T gamma delta cells expressing these antigens could be found. These data suggest that the synovial T gamma delta cells had been activated in vivo.

Adolescent↗
PubMed1994

Characterization of a 10- to 14-kilodalton protease-sensitive Mycobacterium tuberculosis H37Ra antigen that stimulates human gamma delta T cells.

gamma delta T-cell receptor-bearing T cells (gamma delta T cells) are readily activated by intracellular bacterial pathogens such as Mycobacterium tuberculosis. The bacterial antigens responsible for gamma delta T-cell activation remain poorly characterized. We have found that heat treatment of live M. tuberculosis bacilli released into the supernatant an antigen which stimulated human gamma delta T cells. gamma delta T-cell activation was measured by determining the increase in percentage of gamma delta T cells by flow cytometry in peripheral blood mononuclear cells stimulated with antigen and by proliferation of gamma delta T-cell lines with monocytes as antigen-presenting cells. Supernatant from heat-treated M. tuberculosis was fractionated by fast-performance liquid chromatography (FPLC) on a Superose 12 column. Maximal gamma delta T-cell activation was measured for a fraction of 10 to 14 kDa. Separation of the supernatant by preparative isoelectric focusing demonstrated peak activity at a pI of < 4.0. On two-dimensional gel electrophoresis, the 10- to 14-kDa FPLC fraction contained at least seven distinct molecules, of which two had a pI of < 4.5. Protease treatment reduced the bioactivity of the 10- to 14-kDa FPLC fraction for both resting and activated gamma delta T cells. Murine antibodies raised to the 10- to 14-kDa fraction reacted by enzyme-linked immunosorbent assay with antigens of 10 to 14 kDa in lysate of M. tuberculosis. In addition, gamma delta T cells proliferated in response to an antigen of 10 to 14 kDa present in M. tuberculosis lysate. gamma delta T-cell-stimulating antigen was not found in culture filtrate of M. tuberculosis but was associated with the bacterial pellet and lysate of M. tuberculosis. These results provide a preliminary characterization of a 10- to 14-kDa, cell-associated, heat-stable, low-pI protein antigen of M. tuberculosis which is a major stimulus for human gamma delta T cells.

Antigens, Bacterial↗
PubMed1997

Gamma delta cells regulate autoimmunity.

Gamma delta cells are attractive candidates for mediators of autoimmune disease. They can expand in germ-free mice, probably through recognition of autoantigens, and gamma delta-cell-deficient mice, unlike mice deficient in alpha beta T cells or B cells, show no severe defects in the immune response to foreign antigen challenge. A capacity of gamma delta cells to effect or regulate tissue damage is also plausible, given their ready localization to tissues, and their myriad of effector functions. Added to this, attempts to reconstruct the physiological course of autoimmune diseases with only autoreactive alpha beta T cells seem invariably to fall short for lack of other unidentified players. Gamma delta cells and their putative ligands have been linked to autoimmune conditions, and recent experiments confirm that gamma delta cells play a significant role in autoimmune disease in vivo.

Animals↗
PubMed1998

Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL.

NK cells and T cells express killer cell inhibitory receptors (KIR) recognizing polymorphic MHC class I molecules. Although prior studies have established that MHC class I can protect normal and transformed hematopoietic cells from NK cell lysis, the role of MHC class I on the recognition of solid tumors has been controversial. In this study, we investigated whether interactions of KIR with their ligands on melanoma tumor cells could inhibit tumor cell lysis by NK and gamma delta T cell clones. Ligation of the NK cell receptor KIR3DL1 by HLA-Bw4 allotypes resulted in inhibition of cytotoxicity against HLA-B*4403-transfected melanomas as well as against melanomas endogenously expressing HLA-Bw4 allotypes. Similarly, interactions of KIR2DL2 or KIR2DL3 (KIR2DL2/3) with HLA-Cw3-related allotypes on melanomas resulted in decreased tumor cell lysis. We also investigated whether signaling via KIR affected melanoma recognition by CTL. Introduction of KIR3DL1 molecules into HLA-A*0201-restricted gp100-specific CTL resulted in inhibition of lysis of gp100+ melanomas co-expressing HLA-A*0201 and HLA-Bw4 allotypes. These results suggest that disrupting interactions of KIR with their ligands on tumor cells in vivo may enhance antitumor responses mediated by both innate and adaptive immune effector cells.

Animals↗
PubMed2000

Rapid changes occur in the percentage of circulating bovine WC1(+)gamma delta Th1 cells.

gamma delta T cells found in the peripheral blood of cattle include a major subpopulation distinguished by expression of WC1. These cells are distinct from the WC1(-)gamma delta T cell population based on T cell receptor gene usage. We documented that a group of 6-month-old calves allowed free-range grazing and access to their mothers had a significantly greater proportion of total gamma delta T cells in their blood, attributable to the WC1(+)gamma delta T cell subpopulation, compared to age and breed-matched calves held in conventional housing. When the animals with the greater proportion of gamma delta T cells were transferred to conventional housing there was a decrease in the WC1(+)population so that by 3 weeks after transfer there was no longer a significant difference between the two groups. To investigate the biological activities of WC1(+)gamma delta T cells, the cells were purified by flow cytometric sorting. In vitro, they responded to stimulation by irradiated monocytes in autologous mixed leukocyte reaction (AMLR) cultures but not to direct stimulation through the T cell receptor (T c R) by anti-delta monoclonal antibody. After stimulation in the AMLR, WC1(+)gamma delta T cells had a Th1 cytokine profile characterised by production of IFN -gamma and lack of IL -4. Thus we propose that higher levels of the WC1(+)gamma delta T cells may provide calves with a mechanism to produce Th1 cytokines and that the level of these cells may be modulated according to environment or stress since both groups of calves were apparently disease-free.

Animals↗
PubMed1994

Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell.

TCR-gamma delta cells, a T cell subset present in the epithelial and lymphoid tissues, have been implicated in viral and bacterial infections. We have identified a TCR-gamma delta clone (TgI4.4) that, unlike TCR-alpha beta cells, recognizes a herpes simplex virus type 1 transmembrane glycoprotein, gI, in an MHC class I- and class II-independent fashion. The TCR of TgI4.4 is composed of rearranged V delta 8 (a V alpha 2 family member) and V gamma 1.2 variable genes, a heterodimeric pair not previously described. Furthermore, anti-V alpha 2 mAbs are sufficient to block recognition of the gI ligand. Strikingly, anti-gI Abs also are capable of blocking recognition, a phenomena that is very rare in TCR-alpha beta Ag recognition. Therefore, to dissect the mechanism involved in this unique form of Ag recognition, we constructed a mutant of gI, gIt, that lacks cell surface expression upon transfection into APCs. This form of gI was not sufficient for Ag presentation. In contrast, wild-type gI expressed in the Ag-processing mutant cell, RMA-S, is recognized by TgI4.4, suggesting that gI presentation occurs independently of classical Ag-processing pathways. In fact, through the use of a soluble recombinant gI molecule, gI-Ig, we show that TgI4.4 can recognize whole, unprocessed gI protein in the absence of any APCs. These results suggest that there exist alternate and novel forms of TCR Ag recognition, and that the TCR-gamma delta clone, TgI4.4, may represent a novel T cell subset that, during pathogenic challenge, may respond directly to Ags on the surfaces of bacteria and viruses.

Amino Acid Sequence↗
PubMed1989

Immunoregulatory function of CD3+, CD4-, and CD8- T cells. Gamma delta T cell receptor-positive T cells from nude mice abrogate oral tolerance.

Previous work has shown that abrogation of oral tolerance is mediated by T cells which are found in the CD3+, L3T4- (CD4-), and Lyt-2- (CD8-) subset (termed double-negative; DN) in mice. Inasmuch as it is known that athymic, nude (nu/nu) mice possess Thy 1+, CD4-, and CD8- T cells which also exhibit a functionally rearranged TCR gamma-chain, we investigated whether this subset of nude T cells contained functional immunoregulatory cells. In this report, we examined the phenotype and distribution of CD3+ T cells in the spleen and in the mesenteric and peripheral lymph nodes of BALB/c nu/nu mice in comparison with normal mice (+/+). In the spleens of nude mice, the predominant CD3+ T cell subpopulation was DN. Further, in mesenteric and peripheral lymph nodes, approximately one-third and one-half of the CD3+ T cells were double negative, respectively. In contrast, CD3+, DN T cells represent a small subpopulation in normal (+/+) mice. We next showed that functional regulatory T cells which possess the ability to abrogate oral tolerance were induced in nu/nu mice by Ag priming. BALB/c nude mice were immunized with SRBC, and the splenic CD3+, Vicia villosa-adherent cells were obtained by panning. Adoptive transfer of CD3+, V. villosa-adherent T cells to orally tolerant BALB/c mice restored responsiveness to SRBC, whereas V. villosa nonadherent cells were without effect. In other experiments, CD3+ T cells from the spleens of SRBC-primed mice were further enriched for the CD5+, DN phenotype and adoptive transfer of this subset completely abrogated oral tolerance to SRBC. To characterize the nature of the TCR expressed on these CD3+, DN T cells, we developed a rabbit antibody to a synthetic peptide (residues 209-218: Tyr-Ala-Asn-Ser-Phe-Asn-Asn-Glu-Lys-Leu) which was synthesized from a deduced sequence of the murine delta-gene. Immunoprecipitation of a cell membrane fraction from CD3+, DN T cells with anti-delta TCR antibody isolated a 45-kDa band. Furthermore, immunoprecipitation of these cells with anti-CD3 (145-2C11) revealed bands at 45 and 35 kDa (corresponding to delta- and gamma-chains, respectively). Taken together, these results are the first to show that gamma delta-TCR bearing CD3+, CD4-, and CD8- T cells are functional and reverse oral tolerance when adoptively transferred.

Administration, Oral↗
PubMed1994

Changes in epidermal Langerhans cells, gamma delta T cells and CD4 T cells after intradermal infection with recombinant vaccinia virus expressing cytokine genes.

Langerhans cells (LC) play a critical role in cutaneous immunity, and whereas Thy-1+ dendritic epidermal cells (Thy-1+ dEC) are also present in murine epidermis, their role remains unknown. Antigens and cytokines influence the number of LC found in the epidermis. However, there has been no investigation into the effects of particular cytokines during resolution of a viral infection. In order to study this we infected mice subcutaneously with vaccinia virus (VV) constructs containing the genes encoding TNF-alpha, IL-6 or IFN-gamma and the density of LC, THY-1+ dEC and CD4+ cells was determined. In this system the cytokines were produced locally at the site of viral replication. Cell densities were examined at day 1, while the response was being initiated, and at day 5 as the infection was being resolved. Infection with VV, like exposure to other antigens, decreased the density of epidermal LC at day 1, and they remained depressed at day 5. Production of TNF-alpha during VV growth did not influence this response by LC, whereas IFN-gamma and IL-6 both increased the number of epidermal Ia+ LC at day 1 but then caused a reduction at day 5. Thy-1+ dEC were not affected by VV infection at any time-point examined, nor did any cytokine influence the density of these cells at day 1. However, by day 5 IFN-gamma and IL-6, but not TNF-alpha, decreased the number of Thy-1+ dEC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

TCR-gamma delta cells in CD3 zeta-deficient mice contain Fc epsilon RI gamma in the receptor complex but are specifically unresponsive to antigen.

Unlike TCR-alpha beta cells, TCR-gamma delta cells express a distinct member of the zeta family, the gamma-chain of Fc epsilon RI (Fc epsilon RI gamma) within the TCR complex. To study the role of the Fc epsilon RI gamma-chain in TCR-gamma delta cells, a TCR-gamma delta transgenic mouse (G8) has been crossed with CD3 zeta-chain-deficient mice (G8.zeta-/-). Thy-1+ spleen and lymph node cells of these animals expressed low levels of CD3/TCR. These results suggested that the zeta-chain is required for effective TCR transport to the cell surface. In contrast, intraepithelial TCR-gamma delta cells of G8.zeta-/- mice expressed high levels of TCR. Immunoprecipitation with anti-CD3 showed that Fc epsilon RI gamma-chains were associated with the TCR complex in T cells isolated from zeta-deficient mice. Although the Fc epsilon RI gamma-expressing T cells proliferated in response to stimulation by TCR-specific Abs including anti-CD3 epsilon, anti-pan gamma delta, and anti-V gamma 2 mAb, the G8.zeta-/- T cells did not respond to the G8-specific Ag (T10b), anti-Thy-1 mAb, or Con A. The unresponsiveness to the Ag was not due to the reduced TCR expression, because intraepithelial TCR-gamma delta cells from the zeta-deficient mice did not respond to Ag. The inability of the G8.zeta-/- T cells to respond to Ag could not be overcome by providing an anti-CD28 costimulatory signal or by adding exogenous rIL-2. Taken together, our data suggest that the Fc epsilon RI gamma-chain associates with the TCR-gamma delta complex in the absence of the zeta-chain, but it is not able to substitute for the zeta-chain for effective transport of TCR to the cell surface or functional responses to Ag.

Animals↗
PubMed1997

TCR gamma delta+ cells expressing Vgamma 9V delta2, which normally predominate the blood, are found in the spleens of patients with hairy cell leukemia.

T cell receptor gamma delta+ (TCR gamma delta+) cells are present in all lymphoid tissues, but at lower frequencies than TCR alpha beta+ cells. In normal spleens, they account for about 15-20% of CD3+ cells. In hairy cell leukemia (HCL), a B cell malignancy with a characteristic involvement of the spleen, splenic T cells of approximately 40% of the examined patients showed a remarkable increase in CD3+ TCR gamma delta+ cells. Therefore, we studied the TCR gamma delta phenotypes in blood and spleen of 12 HCL patients in comparison with normal samples. In normal blood (n= 6) the majority of TCR gamma delta+ cells expressed the Vgamma 9V delta2 phenotype, while in normal spleens (n = 9) a different population was found expressing Vdelta1. In contrast, six of eight paired blood and spleen samples of individual HCL patients demonstrated the same phenotype with predominantly Vgamma 9V delta2 expression. This change in splenic TCR gamma delta usage in patients with HCL might be the result of cell-trapping, or an infiltration of TCR gamma delta+ cells from the blood.

Humans↗
PubMed2002

The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity.

Granzyme M (GM) is a novel serine protease whose expression is highly restricted to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gamma delta T cells. Using a GM-specific monoclonal antibody, we analyzed the expression of GM in 214 mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal NK/T-cell lymphomas (100%), gamma delta T-cell lymphomas (100%), and intestinal T-cell lymphomas (85%). In contrast, GM expression was present at low prevalence in mycosis fungoides/Sézary syndrome (3%), anaplastic large-cell lymphoma (6%), panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an intermediate frequency (37%) of GM expression, consistent with their heterogeneous origin. We conclude that GM expression is a distinctive feature of the nasal NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and suggest that these tumors develop from lymphocytes involved in innate immunity.

Cell Lineage↗
PubMed2001

Distinct tumour specificity and IL-7 requirements of CD56(-)and CD56(+) subsets of human gamma delta T cells.

gamma delta T cells are believed to recognize tissue injury caused by infections, tumours, as well as chemical and physical agents. The present study was carried out to study the feasibility of the ex vivo expansion of gamma delta T cells from healthy individuals, and to determine their functional capacity against tumours. We selectively expanded the peripheral gamma delta T cells of five donors against a myeloma cell line, XG-7. Under optimal conditions, the resulting bulk cultures comprised about 82% of the gamma delta T cells, more than 90% of which showed the T-cell receptor (TCR)-V gamma 9 delta 2 rearrangement. These gamma delta T-cell cultures exhibited TCR-gamma delta dependent cytotoxicity against different tumour cell lines including Molt-4, BJAB, Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL), and the nasopharyngeal carcinoma (NPC) cell lines, CNE2 and 915, in addition to the stimulator XG-7. By competitive cytotoxicity assays, the gamma delta T cells demonstrated recognition of at least three distinct target specificities expressed by Molt-4, CNE2 and LCL, respectively, which were related to that expressed by the stimulator XG-7 cells. The recognition of the specificity expressed by XG-7 and Molt-4 was further shown to require the participation of heat shock protein (HSP). The specificity expressed by CNE2 and 915 was preferentially recognized by the CD56 subset of gamma delta T cells, which could be sustained in the presence of interleukin (IL)-7. These results suggested that gamma delta T-cell immunity against tumour cell lines may be acquired in response to other types of tissue injury and, hence, implicates a role for their use in the prevention and treatment of tumours.

Burkitt Lymphoma↗
PubMed1991

Human T cell receptor gamma delta + T cells.

TCR gamma delta + T cells represent a minority of CD3+ T cells in many species including man. The molecular structure of the TCR gamma and delta loci in man is well understood. The gamma and delta loci contain V, D, J and C gene segments. These segments do not rearrange randomly but in a coordinated, ordered fashion during thymic development. Therefore, the structure of gamma and delta genes of early fetal TCR gamma delta + thymocytes differ drastically from those in postnatal TCR gamma delta + thymocytes. In contrast to postnatal TCR gamma delta + thymocytes, early fetal-TCR gamma delta + produce substantial levels of IL-4 and IL-5 and the possibility is discussed that the early fetal TCR gamma delta + cells are involved in development of TCR gamma delta + cells. In man, unlike in mouse, no preferential homing of early fetal TCR gamma delta + cells has been observed so far. Mature human peripheral TCR gamma delta + cells can recognize a great variety of cell surface antigens including 'classical' and 'non-classical' MHC antigens, immunoglobulins and other undefined antigens. In addition, TCR gamma delta + can recognize bacterial products. So far, no class of antigens has been defined that is preferentially recognized by TCR gamma delta + T cells and the function of these cells remains elusive.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1994

TCR gamma delta cells: mysterious cells of the immune system.

Gamma delta cells participate in pathogenic infections and autoimmune conditions, yet, almost a decade after their discovery, little is known regarding their TCR repertoire or effector functions. Unlike MHC-restricted antigen recognition employed by TCR alpha beta cells, TCR gamma delta cells can recognize whole unprocessed antigens in an MHC- independent manner. The nature of positive and negative selection used to shape the repertoire of TCR gamma delta cells is unclear, especially in the nonlymphoid tissues where these cells predominate. While TCR gamma delta cells express an activated phenotype and are present in pathological conditions, their roles in immunological protein is unknown. This review will focus on our efforts to study these issues of TCR gamma delta biology.

Animals↗
PubMed1994

Nonpeptide ligands for human gamma delta T cells.

gamma delta T cells respond to a variety of microbial pathogens and transformed cells. Their limited receptor repertoire and activation by mycobacterial antigens resistant to proteases suggest that they may recognize nonpeptide antigens. We have tested a variety of nonpeptide molecules for stimulation of human gamma delta T cells. Synthetic alkyl phosphates, particularly monoethyl phosphate (MEP), selectively activated gamma delta T cells and stimulated their proliferation in vitro. All gamma delta T cells stimulated by MEP expressed V gamma 2/V delta 2 receptors. The purified natural ligand of mycobacteria is chemically similar to, though distinct from, MEP and contains a phosphate residue that is critical for biological activity. Recognition and expansion of a specific T-cell receptor-bearing population to non-peptide ligands is unprecedented among T cells. We suggest that MEP mimics small natural ligands capable of expanding one subset of gamma delta T cells and that this recognition of nonpeptide antigens may play an important role in human immunity to pathogens.

Antibodies↗