scholarly journals Mechanism of self-tolerance of gamma/delta T cells in epithelial tissue.

1992 ◽  
Vol 175 (1) ◽  
pp. 65-70 ◽  
Author(s):  
T A Barrett ◽  
M L Delvy ◽  
D M Kennedy ◽  
L Lefrancois ◽  
L A Matis ◽  
...  
Keyword(s):  
T Cell Receptor ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Epithelial Tissue ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Self Tolerance ◽  
Delta Cells ◽  
Clonal Anergy ◽  
Gamma Delta Cells

The present study examined mechanisms of tolerance for T cell receptor gamma/delta (TCR-gamma/delta) cells. Using a transgenic (Tg) model, we demonstrate that although alloantigen (Ag)-specific TCR-gamma/delta cells are deleted in the thymus and spleen of Ag-bearing mice, intraepithelial lymphocytes (IELs) expressing normal levels of the Tg TCR were present. However, Tg+ IELs from Ag-bearing mice were unresponsive to activation. Furthermore, self-reactive Tg+ IELs decreased in number over time. Thus, in epithelial tissue, Tg TCR-gamma/delta cells are eliminated subsequent to and most likely as a result of the induction of clonal anergy.

scholarly journals A role for interleukin 4 in the differentiation of mature T cell receptor gamma/delta + cells from human intrathymic T cell precursors.

1990 ◽  
Vol 172 (2) ◽  
pp. 439-446 ◽  
Author(s):  
A Bárcena ◽  
M L Toribio ◽  
L Pezzi ◽  
C Martínez
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Critical Role ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Gamma Delta ◽  
Consistent Finding ◽  
Delta Cells ◽  
Gamma Delta Cells

We have analyzed the effect of human recombinant interleukin 4 (rIL-4) on the growth and differentiation of human intrathymic pre-T cells (CD7+2+1-3-4-8-). We describe that this population of T cell precursors proliferates in response to rIL-4 (in the absence of mitogens or other stimulatory signals) in a dose-dependent way. The IL-4-induced proliferation is independent of the IL-2 pathway, as it cannot be inhibited with an anti-IL-2 receptor alpha chain antibody. In our culture conditions, rIL-4 also promotes the differentiation of pre-T cells into phenotypically mature T cells. Although both CD3/T cell receptor (TCR)-alpha/beta + and CD3-gamma/delta + T cells were obtained, the preferential differentiation into TCR-gamma/delta + cells was a consistent finding. These results suggest that, in addition to IL-2, IL-4 plays a critical role in promoting growth and differentiation of intrathymic T cell precursors at early stages of T cell development.

scholarly journals Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1875-1881 ◽  
Author(s):  
D van der Harst ◽  
A Brand ◽  
SA van Luxemburg-Heijs ◽  
YM Kooij-Winkelaar ◽  
FE Zwaan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Delta Cells ◽  
Selective Outgrowth ◽  
Gamma Delta Cells

Before and after bone marrow transplantation (BMT) for hematologic malignancies, peripheral blood mononuclear cells from 10 patients were obtained. The relative and absolute numbers of CD3+ T-cell receptor gamma delta+ (TCR gamma delta+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR gamma delta (anti-TCR gamma delta-1), were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCR gamma delta+ cells. Consistent increased numbers of gamma delta cells up to eightfold the pretransplant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant gamma delta and alpha beta T cells express the CD45RO antigen, which is usually expressed on “memory” cells only. The V-region usage of the TCR gamma delta+ T cells was analyzed using fresh mononuclear cells and MoAbs against known V gamma and V delta regions. For more detailed analysis, CD3+TCR gamma delta+ cells were sorted and cultured in bulk and cloned. Using fresh cells and bulk cultures, mainly V gamma 9+V delta 1-V delta 2+ cells were found during engraftment. Only after 6 weeks post-BMT, V gamma 9-V delta 1+V delta 2- cells appear. Analysis of the V gamma and V delta usage at the clonal level confirmed the observation that early after BMT only V gamma 9+V delta 2+ cells are present, whereas gamma delta T- cell clones expressing other gamma delta TCR phenotypes can only be detected 4 to 6 weeks post-BMT. The predominance of V gamma 9+ cells during early engraftment could be explained by several mechanisms: (A) sequential rearrangements during T-cell development, leading to an early wave of V gamma 9+ cells, or (B) selective outgrowth of preexisting V gamma 9+V delta 2+CD45RO+ TCR gamma delta cells in the bone marrow graft, possibly as a result of antigen driven expansion due to exposure to environmental antigens.

scholarly journals Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1875-1881 ◽  
Author(s):  
D van der Harst ◽  
A Brand ◽  
SA van Luxemburg-Heijs ◽  
YM Kooij-Winkelaar ◽  
FE Zwaan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Delta Cells ◽  
Selective Outgrowth ◽  
Gamma Delta Cells

Abstract Before and after bone marrow transplantation (BMT) for hematologic malignancies, peripheral blood mononuclear cells from 10 patients were obtained. The relative and absolute numbers of CD3+ T-cell receptor gamma delta+ (TCR gamma delta+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR gamma delta (anti-TCR gamma delta-1), were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCR gamma delta+ cells. Consistent increased numbers of gamma delta cells up to eightfold the pretransplant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant gamma delta and alpha beta T cells express the CD45RO antigen, which is usually expressed on “memory” cells only. The V-region usage of the TCR gamma delta+ T cells was analyzed using fresh mononuclear cells and MoAbs against known V gamma and V delta regions. For more detailed analysis, CD3+TCR gamma delta+ cells were sorted and cultured in bulk and cloned. Using fresh cells and bulk cultures, mainly V gamma 9+V delta 1-V delta 2+ cells were found during engraftment. Only after 6 weeks post-BMT, V gamma 9-V delta 1+V delta 2- cells appear. Analysis of the V gamma and V delta usage at the clonal level confirmed the observation that early after BMT only V gamma 9+V delta 2+ cells are present, whereas gamma delta T- cell clones expressing other gamma delta TCR phenotypes can only be detected 4 to 6 weeks post-BMT. The predominance of V gamma 9+ cells during early engraftment could be explained by several mechanisms: (A) sequential rearrangements during T-cell development, leading to an early wave of V gamma 9+ cells, or (B) selective outgrowth of preexisting V gamma 9+V delta 2+CD45RO+ TCR gamma delta cells in the bone marrow graft, possibly as a result of antigen driven expansion due to exposure to environmental antigens.

scholarly journals Thymic origin of embryonic intestinal gamma/delta T cells.

1993 ◽  
Vol 177 (2) ◽  
pp. 257-263 ◽  
Author(s):  
D Dunon ◽  
M D Cooper ◽  
B A Imhof
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Cell Subpopulation ◽  
Current Evidence ◽  
Gamma Delta T Cells ◽  
Intestinal Colonization ◽  
Gamma Delta ◽  
Embryo Cells

Current evidence suggests both thymic and extrathymic origins for T cells. Studies in mice favor an in situ origin for a prominent population of intestinal intraepithelial lymphocytes that express gamma/delta T cell receptor (TCR). This developmental issue is explored in an avian model in which the gamma/delta lymphocytes constitute a major T cell subpopulation that is accessible for study during the earliest stages of lymphocyte development. In the chick embryo, cells bearing the gamma/delta TCR appear first in the thymus where they reach peak levels on days 14-15 of embryogenesis, just 2 d before gamma/delta T cells appear in the intestine. Using two congenic chick strains, one of which expresses the ov antigen, we studied the origin and kinetics of intestinal colonization by gamma/delta T cells. The embryonic gamma/delta+ thymocytes homed to the intestine where they survived for months, whereas an embryonic gamma/delta- thymocyte population enriched in thymocyte precursors failed to give rise to intestinal gamma/delta+ T cells. Embryonic hemopoietic tissues, bone marrow, and spleen, were also ineffective sources for intestinal gamma/delta+ T cells. Intestinal colonization by gamma/delta+ thymocytes occurred in two discrete waves in embryos and newly hatched birds. The data indicate that intestinal gamma/delta T cells in the chicken are primarily thymic migrants that are relatively long-lived.

T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu's arteritis

2006 ◽  
Vol 118 (2-3) ◽  
pp. 243-249 ◽  
Author(s):  
Sunil Kumar Chauhan ◽  
Naresh Kumar Tripathy ◽  
Nakul Sinha ◽  
Soniya Nityanand
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Takayasu’S Arteritis ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

scholarly journals Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1311-1322 ◽  
Author(s):  
G De Libero ◽  
G Casorati ◽  
C Giachino ◽  
C Carbonara ◽  
N Migone ◽  
...  
Keyword(s):  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Single Population ◽  
Complex Molecules ◽  
Histocompatibility Complex ◽  
Gene Usage ◽  
Nested Sets ◽  
Antigen Presenting ◽  
Delta Cells ◽  
Gamma Delta Cells

V gamma 9/V delta 2 cells represent a fraction of human gamma/delta cells that is expanded after birth in the periphery, carries markers of activated cells, and becomes a major population in peripheral blood. We found that these cells do not comprise a single population but actually represent two nested sets, the smaller of which, specific for Mycobacterium tuberculosis-pulsed antigen-presenting cells (APC), is contained in a larger set specific for an antigen found on the Molt-4 lymphoma. The larger set, representing 40-80% of all blood gamma/delta cells, is comprised of cells bearing the V gamma 9/C gamma 1 chain. Cells in the smaller, included set have an additional requirement for V delta 2 (and probably for certain permissive junctional regions, since a very small percentage of V gamma 9/V delta 2 cells do not react against mycobacteria-pulsed APC). Optimal stimulation by mycobacteria is dependent on the presence of APC, and is not restricted by classical major histocompatibility complex molecules. Some of the V gamma 9/V delta 2 mycobacteria-specific clones are also stimulated by APC pulsed with different bacteria, such as Listeria monocytogenes and Escherichia coli, indicating that the population includes several different patterns of reactivity. These data establish a relationship in humans between specificity and V gamma/V delta gene usage, and offer an explanation for the peripheral expansion of these gamma/delta cells.

scholarly journals The primary response of human gamma/delta + T cells to Mycobacterium tuberculosis is restricted to V gamma 9-bearing cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1331-1338 ◽  
Author(s):  
D Kabelitz ◽  
A Bender ◽  
T Prospero ◽  
S Wesselborg ◽  
O Janssen ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Proliferative Response ◽  
Primary Cultures ◽  
Cell Receptor ◽  
Primary Response ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Receptor Phenotype ◽  
Delta Cells

We have previously reported that peripheral blood gamma/delta + T cells proliferate in high frequency (1 in 2-20) in response to heat-killed Mycobacterium tuberculosis (M.tb.). In the present study, the T cell receptor phenotype of mycobacteria-responsive human gamma/delta + T cells was analyzed in primary cultures with a set of monoclonal antibodies (mAbs) directed against V gamma 9, V delta 1, and V delta 2. When unseparated T cells were stimulated with M.tb., all proliferating gamma/delta + T cells expressed V gamma 9 (and V delta 2) after culture. Selective depletion of V gamma 9-bearing cells before culture completely abolished the proliferative response of all gamma/delta + cells (but did not inhibit reactivity of alpha/beta + T cells). In addition, when CD4- CD8- thymocytes were stimulated with M.tb., there was again selective outgrowth of V gamma 9+ cells. In this case, the starting responder population contained few (0.5-1.8%) V gamma 9+ and many (11.5-31.5%) V delta 1+ cells that did not coexpress V gamma 9. These V delta 1+ cells were not activated by M.tb. but could be readily stimulated by anti-V delta 1 mAb A13. Finally, a V gamma 9-specific mAb selectively suppressed the proliferative response of gamma/delta + T cells to M.tb. Taken together, our results demonstrate that, within gamma/delta + T cells, reactivity towards M.tb. is an exclusive property of V gamma 9+/V delta (2+)-bearing cells.

scholarly journals Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function.

1989 ◽  
Vol 170 (5) ◽  
pp. 1569-1581 ◽  
Author(s):  
T Goodman ◽  
L Lefrancois
Keyword(s):  
Functional Programming ◽  
Fluorescence Analysis ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Anatomical Site ◽  
Gamma Delta ◽  
Specific Analysis ◽  
Alpha Beta ◽  
And Function ◽  
Delta Cells

The function and structure of the TCR proteins of intraepithelial lymphocytes (IEL) were examined using a panel of mAbs specific for TCR-gamma/delta. Three subsets of TCR-gamma/delta+ IEL could be detected with five mAbs, termed GL1-GL5. The mAbs were able to trigger lysis via crosslinking of the IEL TCR and all of the subsets were constitutively cytolytic. Immunoprecipitation of IEL TCR proteins revealed that the GL2 mAb reacted only with gamma, delta heterodimers containing high Mr delta chains, while the other mAbs precipitated all of the observed gamma and delta proteins. Two-color fluorescence analysis showed that the GL2+ subset was contained within the larger GL1+ subset. The GL3 and GL4 mAbs appear to be specific for all TCR-gamma/delta while GL2 was V delta 4 specific. Analysis of IEL for TCR-alpha/beta expression demonstrated that approximately 20% of B6 IEL were TCR-alpha/beta+. Interestingly, this population of IEL contained Thy-1- and CT1+ cells, indicating that the unique phenotype of IEL was not restricted to TCR-gamma/delta+ cells. Moreover, the TCR-alpha/beta+ IEL were also constitutively cytolytic, suggesting that the intestinal milieu was controlling the functional programming of IEL regardless of TCR type. The mAbs reported here as well as the ability to exploit the distinct phenotype of IEL should prove useful in determining the function of IEL and the TCR-gamma/delta.

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