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.
N1 - Funding Information:
This work was supported in part by National Multiple Sclerosis Society Grant RG2775-A3, USPHS NIH Research Grants NS 34819, NS30871, NS26543, AI35294, CA40216, AI35225, and a grant from Genetics Institute.
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
C2 - 10996219
AN - SCOPUS:0034703310
SN - 0165-5728
VL - 109
SP - 173
EP - 180
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 2
ER -