CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help

• Published in: The Journal of experimental medicine Vol. 177; no. 6; pp. 1791 - 1796
• Main Authors: HARDING, F. A, ALLISON, J. P
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.06.1993; The Rockefeller University Press
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Surface - immunology; B7-1 Antigen; Biological and medical sciences; CD28 Antigens; CD4-Positive T-Lymphocytes - immunology; CD8 Antigens - immunology; Cell interactions; Cell Line; Cells, Cultured; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Interleukin-2 - pharmacology; Lymphocyte Activation; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; T-Lymphocytes, Cytotoxic - immunology; Ligand; Rodentia; Biological marker; Cytotoxicity; Cell cell interaction; Molecular interaction; Cell subpopulation; Signal transduction; Vertebrata; Mixed cell culture; Mammalia; Transfection; Mouse; T-Lymphocyte
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.177.6.1791

The activation requirements for the generation of CD8+ cytotoxic T cells (CTL) are poorly understood. Here we demonstrate that in the absence of exogenous help, a CD28-B7 interaction is necessary and sufficient for generation of class I major histocompatibility complex-specific CTL. Costimulation is required only during the inductive phase of the response, and not during the effector phase. Transfection of the CD28 counter receptor, B7, into nonstimulatory P815 cells confers the ability to elicit P815-specific CTL, and this response can be inhibited by anti-CD28 Fab or by the chimeric B7-binding protein CTLA4Ig. Anti-CD28 monoclonal antibody (mAb) can provide a costimulatory signal to CD8+ T cells when the costimulatory capacity of splenic stimulators is destroyed by chemical fixation. CD28-mediated signaling provokes the release of interleukin 2 (IL-2) from the CD8+ CTL precursors, as anti-CD28 mAb could be substituted for by the addition of IL-2, and an anti-IL-2 mAb can block the generation of anti-CD28-induced CTL. CD4+ cells are not involved in the costimulatory response in the systems examined. We conclude that CD8+ T cell activation requires two signals: an antigen-specific signal mediated by the T cell receptor, and an additional antigen nonspecific signal provided via a CD28-B7 interaction.