Publication Date:
1994-08-26
Description:
The interaction of B7-related molecules on antigen-presenting cells with CD28 or CTLA-4 antigens on T cells provides a second signal for T cell activation. Selection inhibition of the B7-CD28 or B7-CTLA-4 interactions produces antigen-specific T cell unresponsiveness in vitro and suppresses immune function in vivo. To determine whether selective inhibition of the B7-CD28 or B7-CTLA-4 interactions could suppress spontaneous autoimmune disease, a B7-binding protein was generated by genetic fusion of the extracellular domain of murine CTLA-4 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody (muCTLA4Ig). In lupus-prone NZB/NZW filial generation (F1) mice, treatment with muCTLA4Ig blocked autoantibody production and prolonged life, even when treatment was delayed until the most advanced stage of clinical illness. These findings suggest a possible role for human CTLA4Ig in the treatment of autoimmune diseases in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finck, B K -- Linsley, P S -- Wofsy, D -- New York, N.Y. -- Science. 1994 Aug 26;265(5176):1225-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Francisco.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7520604" target="_blank"〉PubMed〈/a〉
Keywords:
Abatacept
;
Animals
;
Antibodies, Antinuclear/biosynthesis
;
Antibodies, Monoclonal
;
Antigens, CD
;
Antigens, CD80/metabolism
;
Antigens, Differentiation/immunology/metabolism/*therapeutic use
;
B-Lymphocytes/immunology
;
CTLA-4 Antigen
;
Female
;
Humans
;
*Immunoconjugates
;
Immunotherapy
;
Lupus Erythematosus, Systemic/immunology/*therapy
;
Mice
;
Mice, Inbred NZB
;
Mice, Inbred Strains
;
Recombinant Fusion Proteins/therapeutic use
;
T-Lymphocytes/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
