In vitro influenza virus-specific antibody production in man: antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes

Abstract

Cloned human T lymphocytes induced with influenza A virus (A/Texas/1/77) and maintained in continuous culture with T cell growth factor were assayed for helper function in the in vitro production of anti-influenza antibody. Helper function mediated by both cloned helper T cells and normal peripheral blood lymphocytes was highly antigen dose-dependent, requiring lower concentrations than that necessary to induce blastogenesis. Optimal help was observed with 1 X 10(2) cloned T cells per culture, whereas excess helper cells inhibited the response. After culture with influenza A virus-induced cloned helper T cells, the antibodies formed were directed against influenza A and not B virus. Furthermore, the cloned helper T cells despite being specific for matrix protein collaborated in the production of predominantly anti-hemagglutinin antibody, suggesting associative recognition of the two discrete antigens. Cellular interactions between cloned helper cells from an HLA-Dw1,3 DR1,3 individual and erythrocyte rosette-negative cells required HLA-Dw1; DR1 compatibility for the production of specific antibody. This was confirmed by using subclones. Finally, it was observed that supernatants of the cloned helper T cells contained functional activity capable of replacing the parent cells in the production of anti-influenza A virus antibody.