Analysis of the costimulatory requirements for generating human virus-specific in vitro T helper and effector responses

• Published in: Journal of clinical immunology 2001-07, Vol.21 (4), p.293-302
• Main Authors: BLAZEVIC, Vesna, MACTRUBEY, C, SHEARER, Gene M
• Format: Article
• Language: English
• Subjects: Abatacept; Antibodies, Monoclonal - pharmacology; Antigen-Presenting Cells - immunology; Antigens, CD - metabolism; Antigens, Differentiation - pharmacology; B7-1 Antigen - metabolism; B7-2 Antigen; Biological and medical sciences; CD28 Antigens - metabolism; CTLA-4 Antigen; Cytokines - biosynthesis; g-Interferon; Human viral diseases; Humans; Immune Tolerance; Immunoconjugates; Immunologic Memory; In Vitro Techniques; Infectious diseases; Influenza A virus; Influenza A virus - immunology; Lymphocyte Activation; Medical sciences; Membrane Glycoproteins - metabolism; T-Lymphocytes - immunology; Viral diseases; Viral diseases of the respiratory system and ent viral diseases
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1023/A:1010987426835

The present study analyzes the role of CD28-B7-mediated costimulation during in vitro human peripheral blood memory T cell activation by influenza A virus. Inhibition studies using the B7-binding fusion protein CTLA4Ig and antibodies against CD80 and CD86 demonstrate that CTLA4Ig and anti-CD86 inhibited influenza-specific T cell proliferation, interleukin (IL)-2 and interferon (IFN)-gamma production, and generation of influenza-specific CD8+ CTL. The production of IL-10 and IL-18, which are known to modulate T cell immune responses, were not affected by blocking the CD28-B7 costimulatory pathway. Inhibition of diverse influenza-specific T cell functions could be reversed by the addition of exogenous IL-2 or IL-12 but not by the addition of IFN-gamma or IL-18. Although IL-2 is known to overcome CD28-B7 costimulatory requirements, this is the first report showing that exogenous IL-12 is able to bypass CD28-B7 costimulatory blockade induced by CTLA4Ig in vitro. The induction of IFN-gamma production with the recently described IFN-gamma inducing cytokine IL-18 was not detected. In conclusion, these results demonstrate that CD86 represents a major costimulatory signal for the activation of resting peripheral blood memory T cells with recall antigens. These observations may have important implications for the development of immunotherapeutic strategies in diverse immunodeficiency diseases as well as in tumor immunotherapy.