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 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 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.

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 Zoledronic Acid Induces the Proliferation of Human Cord Blood Gamma Delta T Cells Ex Vivo

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1427-1427
Author(s):  
Suzanne L Tomchuck ◽  
Jin He ◽  
Ross W. Perko ◽  
Scarlett Evans ◽  
Amy McKenna ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Fold Increase ◽  
T Cell Proliferation ◽  
Gamma Delta T Cells ◽  
Memory Cells ◽  
Gamma Delta ◽  
Gamma Delta T Cell

Abstract Cord blood (CB) T cells are known to be naïve cells, but can be activated to respond similar to adult peripheral blood (PB) T cells. Reports indicate that culture with aminobisphosphonate (NBP) stimulates CB gamma delta T cell proliferation ex vivo, specifically the TCRγ9δ2 subset, which has been extensively studied in PB gamma delta T cells. As CB gamma delta T cells are not well described, we compared CB gamma delta T cell proliferation, phenotype and genotype to PB gamma delta T cells when culturing cells with the NBP, Zometa (zoledronic acid), and IL-2. Fourteen days in culture resulted in significant fold increase in the proliferation of gamma delta T cells and in the percent of lymphocytes in both sample types. PB gamma delta T cells proliferated more robustly than CB with a 288.60 versus 21.32 fold increase, respectively. Additionally, in freshly isolated samples, CB gamma delta T cells comprised an average of 1.404% of the lymphocyte population, which was similar to PB gamma delta T cells, with an average of 2.319%. However, by day 14, PB gamma delta T cells increased to 70.15% of lymphocytes whereas CB gamma delta T cells increased to 12.49%. Phenotypically, both CB and PB had similar percent of CD45RA+ and CD45RO+ gamma delta T cell memory subsets in freshly isolated samples. Following culture, PB gamma delta T cells were mostly CD45RO+ memory cells, with significantly fewer CD45RA+ naïve cells, whereas more CB gamma delta T cells were of the intermediate CD45RA+CD45RO+ subset. Further phenotypic analysis of the memory subsets indicated that cultured PB gamma delta T cells were either effector memory cells (CD27-CD45RA-) or central memory cells (CD27+CD45RA-), while CB gamma delta T cells were mostly naïve (CD27+CD45RA+). The cytokines secreted by these cells were also assessed and the culture of PB and CB gamma delta T cells resulted in differing cytokine secretion profiles. After 14 days of culture, PB gamma delta T cells secreted more IFNγ and TNFα, while CB gamma delta T cells secreted more IL-10 and RANTES. We also examined TCRγ9 and TCRδ2 phenotypic expression and found that the TCRγ9δ2 was a common clone in freshly isolated PB gamma delta T cells, which predominated after 14 days in culture. However, while the TCRγ9δ2 variant was expressed in CB gamma delta T cells, it was low before and after culture, suggesting that Zometa may not stimulate gamma delta T cells in CB the same as PB. As limited TCRγδ phenotypic reagents are available, we developed a single cell PCR assay for genotypic analysis of the TCRγδ repertoire. PCR analysis suggests that the TCRγδ repertoire is diverse in both samples, yet TCRγ9δ2 is most prevalent. Further analysis of the variant subsets is warranted and may give insight into how each of these receptor pairings affects function. Disclosures No relevant conflicts of interest to declare.

scholarly journals Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor αβ lineage

1998 ◽  
Vol 95 (16) ◽  
pp. 9459-9464 ◽  
Author(s):  
Stephanie T. Page ◽  
Lisa Y. Bogatzki ◽  
Jessica A. Hamerman ◽  
Claire H. Sweenie ◽  
Philip J. Hogarth ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Nude Mice ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Tcr Signaling ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Cell Commitment

The majority of T cells develop in the thymus and exhibit well characterized phenotypic changes associated with their maturation. Previous analysis of intestinal intraepithelial lymphocytes (IEL) from nude mice and a variety of experimentally manipulated models led to the view that at least a portion of these cells represent a distinct T cell population that matures extrathymically. The IEL that are postulated to mature within the intestine include both T cell receptor (TCR) αβ- and γδ-bearing subpopulations. They can be distinguished from conventional thymically derived T cells in that they express an unusual coreceptor, a CD8α homodimer. In addition, they can utilize the Fc receptor γ-chain in place of the CD3-associated ζ-chain for TCR signaling and their maturation depends on the interleukin 2 receptor β-chain. Moreover, TCRαβ+CD8αα+ IEL are not subject to conventional thymic selection processes. To determine whether CD3−CD8αα+ IEL represent precursors of T cells developing extrathymically, we examined IEL from knockout mice lacking the recombination activating gene-1 (rag-1), CD3ɛ, or both Lck and Fyn, in which thymic T cell development is arrested. CD3−CD8αα+CD16+ IEL from all three mutant strains, as well as from nude mice, included cells that express pre-TCRα transcripts, a marker of T cell commitment. These IEL from lck−/−fyn−/− animals exhibited TCR β-gene rearrangement. However, CD3−CD8αα+CD16+ IEL from ɛ-deficient mice had not undergone Dβ-Jβ joining, despite normal rearrangement at the TCRβ locus in thymocytes from these animals. These results revealed another distinction between thymocytes and IEL, and suggested an unexpectedly early role for CD3ɛ in IEL maturation.

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.

scholarly journals Evidence for clonal selection of gamma/delta T cells in response to a human pathogen.

1991 ◽  
Vol 174 (3) ◽  
pp. 683-692 ◽  
Author(s):  
K Uyemura ◽  
R J Deans ◽  
H Band ◽  
J Ohmen ◽  
G Panchamoorthy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clonal Selection ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Intraepithelial Lymphocytes ◽  
Gamma Delta T Cells ◽  
Antigen Receptors ◽  
Gamma Delta ◽  
Selection Of

T cells bearing gamma/delta antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven gamma/delta T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR delta gene expression among human gamma/delta T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of gamma/delta T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the gamma/delta response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens.

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