Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.
Chronic T cell responses, as they occur in rheumatoid arthritis, are complex and are likely to involve many mechanisms. There is a growing body of evidence that, in concert with the T cell antigen receptor signal, CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) are the primary regulators of T cell responses. Whereas CD28 primarily activates T cell processes, CTLA-4 inhibits them. The mechanism for this dichotomy is not fully understood, especially as CD28 and CTLA-4 recruit similar signalling molecules. In addition, recent studies demonstrate that CD28 and CTLA-4 have multiple functions during T cell responses. In particular, CTLA-4 exerts independent distinct effects during different phases of T cell responses that could be exploited for the treatment of rheumatoid arthritis.
Brunner-Weinzierl
Monika C
MC
Molecular Immunology, Deutsches Rheuma-Forschungszentrum Berlin, Germany. monika.brunner@charite.de
Hoff
Holger
H
Burmester
Gerd-R
GR
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001168:Arthritis / Q000209:etiology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human