scholarly journals Structure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4-, CD8- T lymphocytes.

1988 ◽  
Vol 168 (5) ◽  
pp. 1899-1916 ◽  
Author(s):  
J A Bluestone ◽  
R Q Cron ◽  
M Cotterman ◽  
B A Houlden ◽  
L A Matis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Gene Segment ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Human T Cells ◽  
T Cell Lines ◽  
Gamma Delta T Cell ◽  
Delta Cells

Analyses of TCR-bearing murine and human T cells have defined a unique subpopulation of T cells that express the TCR-gamma/delta proteins. The specificity of TCR-gamma/delta T cells and their role in the immune response have not yet been elucidated. Here we examine alloreactive TCR-gamma/delta T cell lines and clones that recognize MHC-encoded antigens. A BALB/c nu/nu (H-2d)-derived H-2k specific T cell line and derived clones were both cytolytic and released lymphokines after recognition of a non-classical H-2 antigen encoded in the TL region of the MHC. These cells expressed the V gamma 2/C gamma 1 protein in association with a TCR-delta gene product encoded by a Va gene segment rearranged to two D delta and one J delta variable elements. A second MHC-specific B10 nu/nu (H-2b) TCR-gamma/delta T cell line appeared to recognize a classical H-2D-encoded MHC molecule and expressed a distinct V gamma/C gamma 4-encoded protein. These data suggest that many TCR-gamma/delta-expressing T cells may recognize MHC-linked antigens encoded within distinct subregions of the MHC. The role of MHC-specific TCR-gamma/delta cells in immune responses and their immunological significance are discussed.

scholarly journals A delta T-cell receptor deleting element transgenic reporter construct is rearranged in alpha beta but not gamma delta T-cell lineages.

1995 ◽  
Vol 15 (12) ◽  
pp. 7022-7031 ◽  
Author(s):  
J Shutter ◽  
J A Cain ◽  
S Ledbetter ◽  
M D Rogers ◽  
R D Hockett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gamma Delta ◽  
Alpha Chain ◽  
Chain Locus ◽  
Discrete Population ◽  
Alpha Beta ◽  
Gamma Delta T Cell

T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell.

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 Immortalization of human T cells expressing T-cell receptor gamma delta by herpesvirus saimiri.

1995 ◽  
Vol 69 (12) ◽  
pp. 8114-8117 ◽  
Author(s):  
M Yasukawa ◽  
Y Inoue ◽  
N Kimura ◽  
S Fujita
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Herpesvirus Saimiri ◽  
Gamma Delta ◽  
Human T Cells

scholarly journals T cells with gamma/delta T cell receptors (TCR) of intestinal type are preferentially expanded in TCR-alpha-deficient lpr mice.

1995 ◽  
Vol 182 (1) ◽  
pp. 233-241 ◽  
Author(s):  
D P Hughes ◽  
A Hayday ◽  
J E Craft ◽  
M J Owen ◽  
I N Crispe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Variable Region ◽  
Fold Increase ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Gamma Delta ◽  
Activation Induced Cell Death ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Gamma Delta T Cell

Fas-mediated apoptosis is essential for activation-induced cell death of alpha/beta T cells, but it is not clear what role, if any, it plays in regulating other components of the immune system. To study the role of Fas in gamma/delta T cell development, Fas-deficient lpr mice were bred with T cell receptor alpha gene-ablated (TCR-alpha-/-) mice to generate mice deficient in one or both genes. The TCR-alpha-/-, lpr/lpr mice had a nearly 10-fold increase in total lymph node cell (LNC) number compared with Fas-intact TCR-alpha-/- mice, because of expansion of TCR-gamma/delta+ and TCR-beta+ cells. In Fas-intact TCR-alpha-/- mice, approximately one third of the LNCs expressed TCR-gamma/delta. These were evenly divided between the CD4-, CD8-alpha+ and the CD4-, CD8- subsets, and rarely expressed the B220 epitope of CD45. In contrast, in TCR-alpha-/-, lpr/lpr mice, TCR-gamma/delta+ cells comprised half of the LNCs and were primarily CD4-, CD8-, and B220+. Moreover, Fas deficiency in TCR-alpha-/- mice caused a preferential expansion of gamma/delta T cells expressing variable region genes characteristic of intestinal intraepithelial lymphocytes. These results demonstrate a role for Fas in regulating the gamma/delta T cell contribution to peripheral lymph nodes. This mechanism may be most important in limiting the access of activated intestinal intraepithelial lymphocytes to the peripheral lymphoid system.

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 gamma/delta T cell-deficient mice have impaired mucosal immunoglobulin A responses.

1996 ◽  
Vol 183 (4) ◽  
pp. 1929-1935 ◽  
Author(s):  
K Fujihashi ◽  
J R McGhee ◽  
M N Kweon ◽  
M D Cooper ◽  
S Tonegawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cholera Toxin ◽  
T Cell Receptor ◽  
Tetanus Toxoid ◽  
Plasma Cells ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Igg Antibody ◽  
Gamma Delta T Cell

Mucosal tissues of mice are enriched in T cells that express the gamma/delta T cell receptor. Since the function of these cells remains unclear, we have compared mucosal immune responses in gamma/delta T cell receptor-deficient (TCRdelta-/-) mice versus control mice of the same genetic background. The frequency of intestinal immunoglobulin (Ig) A plasma cells as well as IgA levels in serum, bile, saliva, and fecal samples were markedly reduced in TCRdelta-/- mice. The TCRdelta-/- mice produced much lower levels of IgA antibodies when immunized orally with a vaccine of tetanus toxoid plus cholera toxin as adjuvant. Conversely, the antigen-specific IgM and IgG antibody responses were comparable to orally immunized control mice. Direct assessment of the cells forming antibodies against the tetanus toxoid and cholera toxin antigens indicated that significantly lower numbers of IgA antibody-producing cells were present in the intestinal lamina propria and Peyer's patches of TCRdelta-/- mice compared with the orally immunized control mice. The selective reduction of IgA responses to ingested antigens in the absence of gamma/delta T cells suggests a specialized role for gamma/delta cells in mucosal immunity.

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