Antigen Feeding Increases Frequency and Antigen-specific Proliferation Ability of Intraepithelial CD4+T Cells in αβ T Cell Receptor Transgenic Mice

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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Age-related changes in CD4 T cells of T cell receptor transgenic mice

Mechanisms of Ageing and Development ◽

10.1016/s0047-6374(96)01826-x ◽

1997 ◽

Vol 93 (1-3) ◽

pp. 95-105 ◽

Cited By ~ 26

Author(s):

Laura Haynes ◽

Phyllis-Jean Linton ◽

Susan L Swain

Keyword(s):

T Cells ◽

T Cell ◽

Transgenic Mice ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Cell Receptor ◽

Age Related ◽

Age Related Changes

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Regulatory CD4+ T Cells Expressing Endogenous T Cell Receptor Chains Protect Myelin Basic Protein–specific Transgenic Mice from Spontaneous Autoimmune Encephalomyelitis

Journal of Experimental Medicine ◽

10.1084/jem.188.10.1883 ◽

1998 ◽

Vol 188 (10) ◽

pp. 1883-1894 ◽

Cited By ~ 234

Author(s):

Danyvid Olivares-Villagómez ◽

Yijie Wang ◽

Juan J. Lafaille

Keyword(s):

T Cells ◽

T Cell ◽

Transgenic Mice ◽

Myelin Basic Protein ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Basic Protein ◽

Cell Receptor ◽

Allelic Exclusion ◽

Autoimmune Encephalomyelitis

The development of T cell–mediated autoimmune diseases hinges on the balance between effector and regulatory mechanisms. Using two transgenic mouse lines expressing identical myelin basic protein (MBP)–specific T cell receptor (TCR) genes, we have previously shown that mice bearing exclusively MBP-specific T cells (designated T/R−) spontaneously develop experimental autoimmune encephalomyelitis (EAE), whereas mice bearing MBP-specific T cells as well as other lymphocytes (designated T/R+) did not. Here we demonstrate that T/R− mice can be protected from EAE by the early transfer of total splenocytes or purified CD4+ T cells from normal donors. Moreover, whereas T/R+ mice crossed with B cell–deficient, γ/δ T cell–deficient, or major histocompatibility complex class I–deficient mice did not develop EAE spontaneously, T/R+ mice crossed with TCR-α and -β knockout mice developed EAE with the same incidence and severity as T/R− mice. In addition, MBP-specific transgenic mice that lack only endogenous TCR-α chains developed EAE with high incidence but reduced severity. Surprisingly, two-thirds of MBP-specific transgenic mice lacking only endogenous TCR-β chains also developed EAE, suggesting that in T/R+ mice, cells with high protective activity escape TCR-β chain allelic exclusion. Our study identifies CD4+ T cells bearing endogenous α and β TCR chains as the lymphocytes that prevent spontaneous EAE in T/R+ mice.

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Airway Inflammation Driven by Antigen-specific Resident Lung CD4+T Cells in αβ -T Cell Receptor Transgenic Mice

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/ajrccm.161.4.9906078 ◽

2000 ◽

Vol 161 (4) ◽

pp. 1340-1348 ◽

Cited By ~ 20

Author(s):

PATRICK G. KNOTT ◽

PAUL R. GATER ◽

CLAUDE P. BERTRAND

Keyword(s):

T Cells ◽

T Cell ◽

Transgenic Mice ◽

Airway Inflammation ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Cell Receptor

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Single-cell analyses of CD4+ T cells from αβ T cell receptor-transgenic mice: a distinct mucosal cytokine phenotype in the absence of transgene-specific antigen

European Journal of Immunology ◽

10.1002/eji.1830270727 ◽

1997 ◽

Vol 27 (7) ◽

pp. 1774-1781 ◽

Cited By ~ 19

Author(s):

Arman Saparov ◽

Charles O. Elson ◽

Denise Devore-Carter ◽

R. Pat Bucy ◽

Casey T. Weaver

Keyword(s):

T Cells ◽

T Cell ◽

Transgenic Mice ◽

Single Cell ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Specific Antigen ◽

Cell Receptor

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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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