High Dose Suppression of Human Anti‐Influenza A Virus Responses Using T Cell Clones

Abstract

Summary. 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 nol require viable T cells. In order lo investigate the mechanism of this form of suppression, IL-2-dependent T cell clones of helper phenotype {CD4 * , HLA-DR' , 1L-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 MemBel 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 histocompatibitity complex (MHC) restricted and did not involve interaction of antigen with the T cell receptor. HLA-DR. CD3 and CDS determinants were excluded as the binding site for the virus by twocolour immunofluoresceni 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 lL-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.

Specificity andin vitrotransfer of the immunosuppressive effectof detergent-disrupted influenza virus vaccine

“…it is often noted to occur in the presence of high doses of antigen (McCaughan et al, 1985;Adams et at., 1987). Furthermore, when studies on immunosuppression are carried out either in vivo or in vitro, using influenza viruses or antigens, the immunosuppressive effect is found to be sub-type specific (Anders McCaughan tv i//.. 1985).…”