Cutting edge: the related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T cell activation.
Optimal T cell activation requires engagement of CD28 with its counterligands B7-1 and B7-2. Inducible costimulator (ICOS) is the third member of the CD28/CTLA4 family that binds a B7-like protein, B7RP-1. Administration of ICOS-Ig attenuates T cell expansion following superantigen (SAg) administration, but fails to regulate either peripheral deletion or anergy induction. ICOS-Ig, but not CTLA4-Ig, uniquely regulates SAg-induced TNF-alpha production, whereas IL-2 secretion is modulated by CTLA4-Ig, but not ICOS-Ig. In contrast, both ICOS and CD28 are required for complete attenuation of IL-4 production. Our data suggest that ICOS and CD28 regulate T cell expansion and that ligation of either CD28 or ICOS can either uniquely regulate cytokine production (IL-2/TNF-alpha) or synergize for optimal cytokine production (IL-4) after SAg administration.
Gonzalo
J A
JA
Department of Biology, Inflammation Division, Millennium Pharmaceuticals, Cambridge, MA 02139, USA.
Delaney
T
T
Corcoran
J
J
Goodearl
A
A
Gutierrez-Ramos
J C
JC
Coyle
A J
AJ
D000069594:Abatacept; D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004768:Enterotoxins / Q000008:administration & dosage / Q000494:pharmacology; D018796:Immunoconjugates; D060889:Inducible T-Cell Co-Stimulator Protein; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D004768:Enterotoxins; C556694:Icos protein, mouse; D018796:Immunoconjugates; D060889:Inducible T-Cell Co-Stimulator Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal; D000069594:Abatacept