CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis

Research output: Contribution to journalArticle

Nitin J. Karandikar, Todd N. Eagar, Carol L. Vanderlugt, Jeffrey A. Bluestone, Stephen D. Miller

During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed 'epitope spreading'. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both inducing and relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalJournal of Neuroimmunology
Volume109
Issue number2
DOIs
StatePublished - Sep 22 2000

PMID: 10996219

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CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. / Karandikar, Nitin J.; Eagar, Todd N.; Vanderlugt, Carol L.; Bluestone, Jeffrey A.; Miller, Stephen D.

In: Journal of Neuroimmunology, Vol. 109, No. 2, 22.09.2000, p. 173-180.

Research output: Contribution to journalArticle

Harvard

Karandikar, NJ, Eagar, TN, Vanderlugt, CL, Bluestone, JA & Miller, SD 2000, 'CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis' Journal of Neuroimmunology, vol. 109, no. 2, pp. 173-180. https://doi.org/10.1016/S0165-5728(00)00322-2

APA

Karandikar, N. J., Eagar, T. N., Vanderlugt, C. L., Bluestone, J. A., & Miller, S. D. (2000). CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 109(2), 173-180. https://doi.org/10.1016/S0165-5728(00)00322-2

Vancouver

Karandikar NJ, Eagar TN, Vanderlugt CL, Bluestone JA, Miller SD. CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. Journal of Neuroimmunology. 2000 Sep 22;109(2):173-180. https://doi.org/10.1016/S0165-5728(00)00322-2

Author

Karandikar, Nitin J. ; Eagar, Todd N. ; Vanderlugt, Carol L. ; Bluestone, Jeffrey A. ; Miller, Stephen D. / CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. In: Journal of Neuroimmunology. 2000 ; Vol. 109, No. 2. pp. 173-180.

BibTeX

@article{36ef7c0e389a401381292ec92cfc4fc2,
title = "CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis",
abstract = "During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed 'epitope spreading'. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both inducing and relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease. (C) 2000 Elsevier Science B.V.",
keywords = "Autoimmunity, CTLA-4, Costimulation, EAE, Epitope Spreading",
author = "Karandikar, {Nitin J.} and Eagar, {Todd N.} and Vanderlugt, {Carol L.} and Bluestone, {Jeffrey A.} and Miller, {Stephen D.}",
year = "2000",
month = "9",
day = "22",
doi = "10.1016/S0165-5728(00)00322-2",
language = "English (US)",
volume = "109",
pages = "173--180",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis

AU - Karandikar, Nitin J.

AU - Eagar, Todd N.

AU - Vanderlugt, Carol L.

AU - Bluestone, Jeffrey A.

AU - Miller, Stephen D.

PY - 2000/9/22

Y1 - 2000/9/22

N2 - During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed 'epitope spreading'. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both inducing and relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease. (C) 2000 Elsevier Science B.V.

AB - During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed 'epitope spreading'. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both inducing and relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease. (C) 2000 Elsevier Science B.V.

KW - Autoimmunity

KW - CTLA-4

KW - Costimulation

KW - EAE

KW - Epitope Spreading

UR - http://www.scopus.com/inward/record.url?scp=0034703310&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034703310&partnerID=8YFLogxK

U2 - 10.1016/S0165-5728(00)00322-2

DO - 10.1016/S0165-5728(00)00322-2

M3 - Article

VL - 109

SP - 173

EP - 180

JO - Journal of Neuroimmunology

T2 - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 2

ER -

ID: 16820818