J Exp Med. 1996 Aug 1;184(2):783-8.

CTLA-4: a negative regulator of autoimmune disease.

Karandikar NJ, Vanderlugt CL, Walunas TL, Miller SD, Bluestone JA.

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Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.

Abstract

CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA-4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.

PMID:: 8760834; [PubMed - indexed for MEDLINE]
PMCID:: PMC2192746

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CTLA-4: a negative regulator of autoimmune disease.

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