Cooperative Roles of CTLA-4 and Regulatory T Cells in Tolerance to an Islet Cell Antigen

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Cooperative Roles of CTLA-4 and Regulatory T Cells in Tolerance to an Islet Cell Antigen. / Walker, Lucy; Eggena, M; Nagabhushanam, V; Barron, L; Chodos, A; Abbas, A.

In: The Journal of Experimental Medicine, Vol. 199, 14.06.2004, p. 1725-30.

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Walker, Lucy ; Eggena, M ; Nagabhushanam, V ; Barron, L ; Chodos, A ; Abbas, A. / Cooperative Roles of CTLA-4 and Regulatory T Cells in Tolerance to an Islet Cell Antigen. In: The Journal of Experimental Medicine. 2004 ; Vol. 199. pp. 1725-30.

Bibtex

@article{cf84b94bb89247fd813bb8ea19460c5a,
title = "Cooperative Roles of CTLA-4 and Regulatory T Cells in Tolerance to an Islet Cell Antigen",
abstract = "Adoptive transfer of ovalbumin (OVA)-specific T cells from the DO.11 TCR transgenic mouse on a Rag(-/-) background into mice expressing OVA in pancreatic islet cells induces acute insulitis and diabetes only if endogenous lymphocytes, including regulatory T cells, are removed. When wild-type OVA-specific/Rag(-/-) T cells, which are all CD25(-), are transferred into islet antigen-expressing mice, peripheral immunization with OVA in adjuvant is needed to induce diabetes. In contrast, naive CTLA-4(-/-)/Rag(-/-) OVA-specific T cells (also CD25(-)) develop into Th1 effectors and induce disease upon recognition of the self-antigen alone. These results suggest that CTLA-4 functions to increase the activation threshold of autoreactive T cells, because in its absence self-antigen is sufficient to trigger autoimmunity without peripheral immunization. Further, CTLA-4 and regulatory T cells act cooperatively to maintain tolerance, indicating that the function of CTLA-4 is independent of regulatory cells, and deficiency of both is required to induce pathologic immune responses against the islet self-antigen.",
author = "Lucy Walker and M Eggena and V Nagabhushanam and L Barron and A Chodos and A Abbas",
year = "2004",
month = jun,
day = "14",
doi = "10.1084/jem.20040124",
language = "English",
volume = "199",
pages = "1725--30",
journal = "The Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",

}

RIS

TY - JOUR

T1 - Cooperative Roles of CTLA-4 and Regulatory T Cells in Tolerance to an Islet Cell Antigen

AU - Walker, Lucy

AU - Eggena, M

AU - Nagabhushanam, V

AU - Barron, L

AU - Chodos, A

AU - Abbas, A

PY - 2004/6/14

Y1 - 2004/6/14

N2 - Adoptive transfer of ovalbumin (OVA)-specific T cells from the DO.11 TCR transgenic mouse on a Rag(-/-) background into mice expressing OVA in pancreatic islet cells induces acute insulitis and diabetes only if endogenous lymphocytes, including regulatory T cells, are removed. When wild-type OVA-specific/Rag(-/-) T cells, which are all CD25(-), are transferred into islet antigen-expressing mice, peripheral immunization with OVA in adjuvant is needed to induce diabetes. In contrast, naive CTLA-4(-/-)/Rag(-/-) OVA-specific T cells (also CD25(-)) develop into Th1 effectors and induce disease upon recognition of the self-antigen alone. These results suggest that CTLA-4 functions to increase the activation threshold of autoreactive T cells, because in its absence self-antigen is sufficient to trigger autoimmunity without peripheral immunization. Further, CTLA-4 and regulatory T cells act cooperatively to maintain tolerance, indicating that the function of CTLA-4 is independent of regulatory cells, and deficiency of both is required to induce pathologic immune responses against the islet self-antigen.

AB - Adoptive transfer of ovalbumin (OVA)-specific T cells from the DO.11 TCR transgenic mouse on a Rag(-/-) background into mice expressing OVA in pancreatic islet cells induces acute insulitis and diabetes only if endogenous lymphocytes, including regulatory T cells, are removed. When wild-type OVA-specific/Rag(-/-) T cells, which are all CD25(-), are transferred into islet antigen-expressing mice, peripheral immunization with OVA in adjuvant is needed to induce diabetes. In contrast, naive CTLA-4(-/-)/Rag(-/-) OVA-specific T cells (also CD25(-)) develop into Th1 effectors and induce disease upon recognition of the self-antigen alone. These results suggest that CTLA-4 functions to increase the activation threshold of autoreactive T cells, because in its absence self-antigen is sufficient to trigger autoimmunity without peripheral immunization. Further, CTLA-4 and regulatory T cells act cooperatively to maintain tolerance, indicating that the function of CTLA-4 is independent of regulatory cells, and deficiency of both is required to induce pathologic immune responses against the islet self-antigen.

UR - http://www.scopus.com/inward/record.url?scp=3042592443&partnerID=8YFLogxK

U2 - 10.1084/jem.20040124

DO - 10.1084/jem.20040124

M3 - Article

C2 - 15210748

VL - 199

SP - 1725

EP - 1730

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

SN - 0022-1007

ER -