T cell help in human antigen-specific antibody responses can be replaced by interleukin 2.
Recombinant IL 2, and immunosorbent/high performance liquid chromatography-purified interleukin 2 (IL 2) obtained from the human T cell leukemic line Jurkat, but not interferon-alpha or -gamma, were able to substitute for T cells in specific antibody responses to influenza virus by T cell-depleted (E-) human peripheral blood mononuclear cells, and resulted in antibody formation equivalent to that obtained in the presence of T cells. The antibody response was shown to be antigen specific by using two non-cross-reacting strains of influenza virus (A/X31 and B/HK). IL 2 in this assay therefore functions as a T cell-replacing factor. Less than 1% of T (UCHT1+) cells were present in the E- preparations, and this number did not increase during the 7-day culture with antigen and IL 2. Because the frequency of T helper cells for X31 is known to be less than 5 X 10(-5), this low number of contaminating cells excluded indirect action of IL 2 through antigen-specific T helper cells. Three to four times less IL 2 was required for antibody production by E- cells than was needed for optimal proliferation by an IL 2-dependent T cell line. Moreover, the concentration of anti-Tac required for 50% inhibition of the IL 2-induced antibody response was 50 times less than required for 50% inhibition of IL 2-dependent proliferation by the T cell line. But when T cells were added back to the E- cells, the anti-Tac inhibition curve shifted back to that obtained with the T cell line. In cell labeling experiments, Leu 11+ cells but not HNK1+ cells were increased in E- cells cultured with antigen and IL 2. This increase in Leu 11+ cells was abolished by prior passage of the E- cells through Sephadex G-10 columns without affecting the IL 2-induced antibody response. From these experiments we conclude that IL 2 can replace T cells in specific antibody responses, and that the IL 2 effect is not mediated indirectly through T cells or large granular lymphocytes.
D000917:Antibody Formation / Q000187:drug effects*; D000941:Antigens / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000941:Antigens; D000954:Antigens, Surface; D007376:Interleukin-2; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7