TY - JOUR
T1 - Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE
AU - Miller, Stephen D.
AU - Vanderlugt, Carol L.
AU - Lenschow, Deborah J.
AU - Pope, Jonathan G.
AU - Karandikar, Nitin J.
AU - Dal Canto, Mauro C.
AU - Bluestone, Jeffrey A.
N1 - Funding Information:
The authors thank Drs. W. J. Karpus, C. Thompson, A. Sperling, and K. Nikcevich for their thoughtful reviews of the manuscript. This work was supported in part by United States Public Health Service National Institutes of Health research grants NS30671, NS26543, Al35294, CA40216, Al35225 and a grant from Repligen Corporation. J. G. P. is a Howard Hughes Medical Institute predoctoral fellow.
PY - 1995/12
Y1 - 1995/12
N2 - Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP139-151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP179-191 (epitope spreading). In this study, we have determined that the CD28/B7 costimulatory pathway is involved in this process. We found preferential up-regulation of B7-1 during the course of R-EAE and a selective increase in its functional costimulatory activity, relative to B7-2. Anti B7-1 F(ab) fragment therapy, but not anti B7-2 MAb therapy, blocked clinical relapses, ameliorated CNS pathology, and blocked epitope spreading. These results suggest that the maintenance of autoimmune reactivity in EAE depends on CD28/B7-1-dependent costimulation of newly recruited T cells responsible for epitope spreading. These studies have important implications for the role of epitope spreading in disease progression and the clinical application of costimulatory antagonists in autoimmune diseases.
AB - Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP139-151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP179-191 (epitope spreading). In this study, we have determined that the CD28/B7 costimulatory pathway is involved in this process. We found preferential up-regulation of B7-1 during the course of R-EAE and a selective increase in its functional costimulatory activity, relative to B7-2. Anti B7-1 F(ab) fragment therapy, but not anti B7-2 MAb therapy, blocked clinical relapses, ameliorated CNS pathology, and blocked epitope spreading. These results suggest that the maintenance of autoimmune reactivity in EAE depends on CD28/B7-1-dependent costimulation of newly recruited T cells responsible for epitope spreading. These studies have important implications for the role of epitope spreading in disease progression and the clinical application of costimulatory antagonists in autoimmune diseases.
UR - http://www.scopus.com/inward/record.url?scp=0029553431&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029553431&partnerID=8YFLogxK
U2 - 10.1016/1074-7613(95)90063-2
DO - 10.1016/1074-7613(95)90063-2
M3 - Article
C2 - 8777719
AN - SCOPUS:0029553431
SN - 1074-7613
VL - 3
SP - 739
EP - 745
JO - Immunity
JF - Immunity
IS - 6
ER -