High dose suppression of human anti-influenza A virus responses using T cell clones.
Human T cells exposed to high concentrations of influenza A virus cause specific suppression of the in vitro antibody response to the virus, but the phenomenon does not require viable T cells. In order to investigate the mechanism of this form of suppression, IL-2-dependent T cell clones of helper phenotype (CD4+, HLA-DR+, IL-2R+) were prepared with specificity for influenza A (Mem/Bel) and B (B HK) viruses and the non-crossreacting antigen purified protein derivative (PPD). When pulsed with high dose Mem/Bel virus, all three clones transferred suppression equally well to effector cultures of syngeneic or allogeneic E+ and E- cells stimulated with an immunogenic dose of the same virus. Thus, although suppression was specific at the level of expression, the induction phase was non-specific and non-major histocompatibility complex (MHC) restricted and did not involve interaction of antigen with the T cell receptor. HLA-DR, CD3 and CD8 determinants were excluded as the binding site for the virus by two-colour immunofluorescent staining and flow cytometric analysis. The concentrations of antigen required for high dose suppression inhibited antigen-specific proliferation by the clones; on the other hand, they remained partially sensitive to IL-2 and could still release gamma-interferon. These findings suggest that this phenomenon is distinct from conventional antigen-specific suppression mediated by CD8 T cells, but may play a biologically important role in regulating immune responses at least to viral antigens.
D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D011991:Receptors, Virus; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D011991:Receptors, Virus; D007371:Interferon-gamma