Cutting Edge: The Related Molecules CD28 and Inducible Costimulator Deliver Both Unique and Complementary Signals Required for Optimal T Cell Activation

• Published in: The Journal of immunology (1950) Vol. 166; no. 1; pp. 1 - 5
• Main Authors: Gonzalo, Jose-Angel, Delaney, Tracy, Corcoran, Justin, Goodearl, Andrew, Gutierrez-Ramos, Jose Carlos, Coyle, Anthony J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.01.2001
• Subjects: Abatacept; Adjuvants, Immunologic - physiology; Animals; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - pharmacology; Antigens, CD; Antigens, Differentiation - pharmacology; Antigens, Differentiation, T-Lymphocyte - physiology; CD28 Antigens - physiology; Cells, Cultured; Clonal Anergy - immunology; Clonal Deletion - immunology; CTLA-4 Antigen; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Enterotoxins - administration & dosage; Enterotoxins - pharmacology; Immunoconjugates; Inducible T-Cell Co-Stimulator Protein; Injections, Intravenous; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Signal Transduction - immunology; Staphylococcus aureus - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.1.1

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.