Modulation of cytokine expression by CD4+ T cells during coxsackievirus B3 infections of BALB/c mice initiated by cells expressing the gamma delta + T-cell receptor.

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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High Proportion of Gamma-Delta T Cell Receptor Positive T Cells in Bronchoalveolar Lavage and Peripheral Blood of HIV-lnfected Patients with Pneumocystis carinii Pneumonias

Respiration ◽

10.1159/000196194 ◽

1993 ◽

Vol 60 (3) ◽

pp. 170-177 ◽

Cited By ~ 16

Author(s):

Martin K. Kägi ◽

Walter Fierz ◽

Peter J. Grob ◽

Erich W. Russi

Keyword(s):

T Cells ◽

T Cell ◽

Bronchoalveolar Lavage ◽

T Cell Receptor ◽

Peripheral Blood ◽

Pneumocystis Carinii ◽

Cell Receptor ◽

Gamma Delta ◽

Gamma Delta T Cell

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Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor.

Journal of Experimental Medicine ◽

10.1084/jem.176.6.1785 ◽

1992 ◽

Vol 176 (6) ◽

pp. 1785-1789 ◽

Cited By ~ 41

Author(s):

G Pluschke ◽

D Rüegg ◽

R Hohlfeld ◽

A G Engel

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

T Cell Receptor ◽

Cell Clone ◽

Cell Receptor ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

T Cell Clone ◽

Gamma Delta T Cell

Polymyositis mediated by gamma/delta T cells is a unique disease in which autoaggressive T lymphocytes surround, invade, and destroy muscle fibers. Histochemically, the vast majority of muscle-infiltrating T cells in a patient with polymyositis were reactive with a pan-gamma/delta T cell receptor (TCR)-specific monoclonal antibody (TCR-delta 1+), but unlike > 90% of peripheral blood gamma/delta T cells, these lymphocytes did not react with V delta 1- or V gamma 9-specific antibodies (A13- and Ti gamma A-, respectively). Differential reactivity with two different V delta 2-specific monoclonal antibodies (BB3-/TiV-delta 2+) indicated that the infiltrating T cells express a V delta 2-containing TCR with unusual additional structural features. Using conventional and anchored polymerase chain reaction for the analysis of TCR transcripts, we found a striking predominance of one unusual V delta 2-J delta 3 recombination and one V gamma 3-J gamma 1 recombination. Both the unusual phenotype (TCR-delta 1+/A13-/Ti gamma A-/BB3-/TiV-delta 2+) and the dominance of distinct TCR transcripts are compatible with the assumption that one T cell clone, which expresses a V gamma 3-J gamma 1-C gamma 2/V delta 2-J delta 3-C delta disulfide-linked TCR, dominates among the infiltrating T cells of the polymyositis muscle specimen analyzed.

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Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22052713 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2713

Author(s):

Sun-Hye Shin ◽

Kyung-Ah Cho ◽

Hee-Soo Yoon ◽

So-Yeon Kim ◽

Hee-Yeon Kim ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Acyl Chain ◽

Signal Strength ◽

Cell Receptor ◽

Ceramide Synthase ◽

Asthmatic Patients

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

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Functional Uncoupling of T-cell Receptor Engagement and Lck Activation in Anergic Human Thymic CD4+T Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m101072200 ◽

2001 ◽

Vol 276 (20) ◽

pp. 17455-17460 ◽

Cited By ~ 12

Author(s):

Wakae Fujimaki ◽

Makio Iwashima ◽

Junji Yagi ◽

Hua Zhang ◽

Hisako Yagi ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Cell Receptor

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

Journal of Experimental Medicine ◽

10.1084/jem.168.5.1899 ◽

1988 ◽

Vol 168 (5) ◽

pp. 1899-1916 ◽

Cited By ~ 147

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.

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CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer

Journal of Experimental Medicine ◽

10.1084/jem.20011845 ◽

2002 ◽

Vol 196 (4) ◽

pp. 481-492 ◽

Cited By ~ 62

Author(s):

Kristin V. Tarbell ◽

Mark Lee ◽

Erik Ranheim ◽

Cheng Chi Chao ◽

Maija Sanna ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Transgenic Mice ◽

T Cell Receptor ◽

Glutamic Acid Decarboxylase ◽

Cd4 T Cells ◽

Cell Receptor ◽

Acid Decarboxylase ◽

Gad 65

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286–300 (p286) of GAD65. These mice have GAD65-specific CD4+ T cells, as shown by staining with an I-Ag7(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-10 when stimulated in vitro with GAD65 peptide 286–300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4+ T cells, or p286-tetramer+CD4+ Tcells, from GAD65 286–300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286–300-specific T cells have disease protective capacity and are not pathogenic.

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