Epitopes described in "CTLA-4: a negative regulator of autoimmune disease."

Article Authors:N J Karandikar; C L Vanderlugt; T L Walunas; S D Miller; J A Bluestone
Article Title:CTLA-4: a negative regulator of autoimmune disease.
Reference Detail
Reference ID:1015670
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.
Reference Type:Literature
PubMed ID:8760834
Journal:J Exp Med
Journal Volume:184
Article Pages:783-8
Journal ISSN:1540-9538
Article Chemical List:Antigens, CD;Antigens, Differentiation;Autoantigens;CTLA-4 Antigen;Ctla4 protein, mouse;Immunoconjugates;Interleukin-2;Myelin Basic Protein;Peptides;abatacept;Interferon-gamma
Article MeSH List:Amino Acid Sequence; Animals; Antigens, CD; Antigens, Differentiation(physiology); Autoantigens(immunology); CTLA-4 Antigen; Encephalomyelitis, Autoimmune, Experimental(immunology); Female; Immunization, Passive; Immunoconjugates; Interferon-gamma(biosynthesis); Interleukin-2(biosynthesis); Lymphocyte Activation; Mice; Mice, Inbred Strains; Molecular Sequence Data; Myelin Basic Protein(chemistry; immunology); Peptides(chemistry; immunology)
Curation Last Updated:2015-07-30 20:31:34