Human T-cell recognition of Listeria monocytogenes: recognition of listeriolysin O by TcR alpha beta + and TcR gamma delta + T cells.

We have previously reported that T cells bearing T cell receptors (TCRs) of gamma/delta type appear at a relatively early stage of primary infection with Listeria monocytogenes in mice. To characterize the early-appearing gamma/delta T cells during listeriosis, we analyzed the specificity and cytokine production of the gamma/delta T cells in the peritoneal cavity in mice inoculated intraperitoneally with a sublethal dose of L. monocytogenes. The early-appearing gamma/delta T cells, most of which were of CD4-CD8- phenotype, proliferated and secreted IFN-gamma and macrophage chemotactic factor in response to purified protein derivative from Mycobacterium tuberculosis, or recombinant 65-kD heat-shock protein derived from M. bovis but not to heat-killed Listeria. To further elucidate the potential role of the gamma/delta T cells in the host-defense mechanism against primary infection with Listeria, we examined the effects of in vivo administration of monoclonal antibodies (mAbs) against TCR-gamma/delta or TCR-alpha/beta on the bacterial eradication in mice infected with Listeria. Most of alpha/beta T cells or gamma/delta T cells were depleted in the peripheral lymphoid organs at least for 12 d after an intraperitoneal injection of 200 micrograms TCR-alpha/beta mAb or 200 micrograms TCR-gamma/delta mAb, respectively. An exaggerated bacterial multiplication was evident at the early stage of listerial infection in the gamma/delta T cells-depleted mice, whereas the alpha/beta T cell-depleted mice exhibited much the same resistance level as the control mice at this stage although the resistance was severely impaired at the late stage after listerial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

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Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.

Journal of Experimental Medicine ◽

10.1084/jem.183.5.2271 ◽

1996 ◽

Vol 183 (5) ◽

pp. 2271-2282 ◽

Cited By ~ 87

Author(s):

L Wen ◽

W Pao ◽

F S Wong ◽

Q Peng ◽

J Craft ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lupus Erythematosus ◽

Cell Receptor ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Autoantibody Production ◽

Ige Synthesis ◽

Alpha Beta ◽

T Cell Help

The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency.

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A gamma/delta cell receptor heterodimer induces the expression of CD4 and CD8 in thymocytes.

Journal of Experimental Medicine ◽

10.1084/jem.174.1.293 ◽

1991 ◽

Vol 174 (1) ◽

pp. 293-296 ◽

Cited By ~ 13

Author(s):

M Iwashima ◽

M M Davis ◽

Y H Chien

Keyword(s):

T Cells ◽

T Cell ◽

Cell Receptor ◽

Surface Expression ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Double Positive ◽

Continuous Surface ◽

Delta Cell ◽

Alpha Beta

CD4 and CD8 have been useful surface markers for alpha/beta T cell maturation. In an alpha/beta T cell receptor (TCR) transgenic SCID mice system, it has been shown that alpha/beta TCR alone is sufficient to induce CD4 and CD8 surface expression on thymic T cells. Although the late embryonic thymic gamma/delta T cells are predominately single and double positive, it has not been clear if gamma/delta TCR has a similar capacity. In this study, we show that when transgenes encoding the earliest embryonic gamma/delta TCR are coexpressed with the SCID defect, the gamma/delta transgenes promote the appearance of both the CD4-8- and CD4+8+ T cells in the thymus. Furthermore, the expression of CD4 and CD8 does not require continuous surface gamma/delta TCR expression. These results indicate that gamma/delta TCR alone can promote the CD4/8 surface expression, and may suggest a role for gamma/delta T cells in initiating normal thymic ontogeny.

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Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells.

Journal of Experimental Medicine ◽

10.1084/jem.178.3.985 ◽

1993 ◽

Vol 178 (3) ◽

pp. 985-996 ◽

Cited By ~ 43

Author(s):

M J Skeen ◽

H K Ziegler

Keyword(s):

T Cells ◽

T Cell ◽

Cell Population ◽

T Cell Subsets ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Accessory Cells ◽

Alpha Beta ◽

Gamma Delta T Cell

Peritoneal gamma/delta T cells from Listeria-immune mice show an enhanced potential to expand when restimulated with antigens or mitogens in vitro (see companion paper [Skeen, M. J., and H. K. Ziegler. 1993. J. Exp. Med. 178:971]). When cocultured with peritoneal alpha/beta T cells, the gamma/delta T cell population expanded preferentially even when the in vitro stimulus was specific for the alpha/beta T cell population. Purified gamma/delta T cells did not respond to alpha/beta T cell-specific stimuli. If isolated T cell subsets were recombined in cell mixing experiments, the resulting proliferative response was greater than additive. Irradiated alpha/beta T cells could enhance the proliferation of responding gamma/delta T cells, but the effect was unidirectional; i.e., irradiated gamma/delta T cells did not stimulate responding gamma/delta T cells. This effect appeared to be cytokine mediated and did not require cell-cell contact. Both recombinant interleukin 2 (rIL-2) and rIL-7 could support the expansion of the gamma/delta T cells, while rIL-7 was only minimally stimulatory for the alpha/beta T cells. The magnitude of the response by gamma/delta T cells to rIL-7 exceeded the response to other in vitro stimuli, including immobilized anti-T cell receptor monoclonal antibody, and was 50-100-fold greater than the alpha/beta T cell response to IL-7. This unique sensitivity of gamma/delta T cells to IL-7 was strongly enhanced by the presence of accessory cells. These cells could be replaced by rIL-1, establishing a synergy for IL-1 and IL-7 as factors that could uniquely stimulate this gamma/delta T cell population. Isolated peritoneal gamma/delta T cells from Listeria-immune mice react to heat-killed Listeria preparations in the presence of macrophages accessory cells in a non-H-2-restricted manner. Considered collectively, these results suggest a potential mechanism by which gamma/delta T cells can predominate in epithelial tissues and at sites of infection.

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Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell precursors.

Journal of Experimental Medicine ◽

10.1084/jem.168.6.2231 ◽

1988 ◽

Vol 168 (6) ◽

pp. 2231-2249 ◽

Cited By ~ 28

Author(s):

M L Toribio ◽

A de la Hera ◽

J Borst ◽

M A Marcos ◽

C Márquez ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Interleukin 2 ◽

Cell Receptor ◽

Beta Chain ◽

Gamma Delta ◽

Human T Cell ◽

Alpha Beta ◽

A Minor

In this report, we have undertaken the phenotypic, functional and molecular characterization of a minor (less than 5%) subpopulation of adult thymocytes regarded as the earliest intrathymic T-cell precursors. Pro-T cells were immunoselected and shown to express different hematopoietic cell markers (CD45, CD38, CD7, CD5) and some activation-related molecules (4F2, Tr, HLA class II), but lack conventional T cell antigens (CD2-1-3-4-8-). TCR-gamma RNA messages are already expressed at this early ontogenic stage, while alpha and beta chain TCR genes remain in germline configuration. In vitro analyses of the growth requirements of pro-T cells demonstrated the involvement of the IL-2 pathway in promoting their proliferation and differentiation into CD3+ CD4+ or CD8+ mature thymocytes. Moreover, during the IL-2-mediated maturation process rearrangements and expression of both alpha and beta chain TCR genes occurred, and resulted in the acquisition of alpha/beta as well as gamma/delta (either disulphide-linked or non-disulphide-linked) heterodimeric TCR among the pro-T cell progeny.

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Interactions of human alpha/beta and gamma/delta T lymphocyte subsets in shear flow with E-selectin and P-selectin.

Journal of Experimental Medicine ◽

10.1084/jem.183.3.1193 ◽

1996 ◽

Vol 183 (3) ◽

pp. 1193-1203 ◽

Cited By ~ 45

Author(s):

T G Diacovo ◽

S J Roth ◽

C T Morita ◽

J P Rosat ◽

M B Brenner ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

Cell Populations ◽

Slight Reduction ◽

Gamma Delta T Cells ◽

Flow Conditions ◽

Gamma Delta ◽

Alpha Beta ◽

Static Conditions

We have compared the ability of human alpha/beta and gamma/delta T lymphocytes to adhere to selectin-bearing substrates, an interaction thought to be essential for homing and localization at sites of inflammation. Both T cell populations form rolling adhesions on E- and P-selectin substrates under physiologic flow conditions. Although equivalent to alpha/beta T cells in binding to E-selectin, gamma/delta T cells demonstrated greater ability to adhere to P-selectin that was purified or expressed on the surface of activated, adherent platelets. Under static conditions, 80% of gamma/delta T cells and 53% of alpha/beta T cells formed shear-resistant adhesions to P-selectin, whereas only 30% of gamma/delta and alpha/beta T cells adhered to E-selectin. The enhance ability of gamma/delta T cells to adhere to P-selectin cannot be attributed to differences in expression of the P-selectin glycoprotein ligand (PSGL-1), as all alpha/beta T cells versus approximately 75% of gamma/delta T cells expressed PSGL-1. Both cell populations expressed a similar percentage of the carbohydrate antigens sialyl LewisX and cutaneous lymphocyte-associated antigen. Depletion of lymphocyte populations or T cell clones bearing these oligosaccharides with the monoclonal antibody CSLEX-1 and HECA-452, respectively, resulted in a substantial reduction in adhesion to E-selectin and slight reduction in adhesion to P-selectin under flow conditions. Treatment of cells with an endopeptidase that selectively degrades O-sialomucins such as PSGL-1, abolished P-selectin but not E-selectin adhesion. Removal of terminal sialic acids with neuraminidase or protease treatment of cells abrogated cell adhesion to both selectin substrates. These results provide direct evidence for the presence of distinct E- and P-selectin ligands on T lymphocytes and suggest that gamma/delta T cells may be preferentially recruited to inflammatory sites during the early stages of an immune response when P-selectin is upregulated.

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Rearrangement of the T-cell receptor delta genes in human T-cell leukemias

Blood ◽

10.1182/blood.v73.2.559.559 ◽

1989 ◽

Vol 73 (2) ◽

pp. 559-565 ◽

Cited By ~ 32

Author(s):

L Foroni ◽

M Laffan ◽

T Boehm ◽

TH Rabbitts ◽

D Catovsky ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Germ Line ◽

Lymphoblastic Leukemia ◽

Lymphocytic Leukemia ◽

Chain Gene ◽

Gamma Delta ◽

Human T Cell ◽

Delta Gene ◽

Alpha Beta

Abstract Two distinct types of T-cell receptors (TCR), designated alpha beta and gamma delta, have been identified on the surface of T cells. In the adult, T cells bearing the gamma delta TCR are a minority and they have the phenotype CD3+, CD4-, CD8-/+. By using appropriate probes, rearrangements of the TCR alpha, beta, and gamma genes have been extensively investigated in a variety of lymphoproliferative disorders. Because the TCR delta gene has been cloned only recently, no comparable information exists with respect to this in human leukemias. We report the analysis of the TCR delta gene configuration in 21 T-cell acute and chronic leukemias, 40 B-cell leukemias, 4 acute myeloid leukemias of difficult classification, and 12 normal controls. The TCR delta genes were structurally modified in all T-cell disorders and in germ-line configuration in all controls and all but one case of non-T-cell leukemias tested. In one case of T-chronic lymphocytic leukemia (CD3+, CD4-, CD8+) we found rearrangement and expression of TCR gamma and delta (but not alpha and beta), suggesting that leukemic transformation took place in a cell bearing a TCR gamma delta rather than a TCR alpha beta. In two cases of pre-T-acute lymphoblastic leukemia, only delta was rearranged out of the three TCR genes tested. This finding is in keeping with the suggestion that the TCR delta gene might be the first to rearrange in T cell ontogeny, and that its mode of rearrangement may play a role in the subsequent choice of the cell between production of a TCR alpha beta or gamma delta. Thus, TCR delta chain gene analysis can provide novel information of the clonal nature of T-cell disorders, particularly if the analysis of the beta and gamma genes has not been helpful.

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