title: Antigenically activated helper T cells are required as stimulator cells for optimal activation of cytotoxic T lymphocytes under conditions of limiting helper factors.
abstract: This paper deals with the question of how antigenically activated helper cells interact with cytotoxic T-lymphocyte (CTL) precursor cells in an environment where helper factor is limiting. Experiments in culture systems with limiting concentrations of helper factor indicated that the (optimal) activation of CTL required antigenically activated helper T cells as stimulator cells. These experiments were performed partly in macrocultures which contained prostaglandin E2 (PGE2) and partly in microcultures with small numbers of responder cells and without additional helper factors. The results showed that a strong activation of CTL against TNP-haptenated syngeneic or semiallogeneic cells occurred only if the cultures contained TNP-haptenated stimulator cells from euthymic but not athymic donors and if the haptenated stimulator cells were exposed to allogeneic determinants. Moreover, combinations of F1-hybrid stimulator cells and parental responder cells generated no substantial cytotoxic responses against determinants of the other parent, unless the cultures were supplemented with a source of I-region determinants which were foreign to the semiallogeneic stimulator cells. Strong responses against haptenated syngeneic or semiallogeneic stimulator cells were obtained, however, when helper factors were added to the cultures. It was concluded that our cultures with limiting concentrations of helper factors required a close proximity between helper T cells and CTL precursor cells; and this proximity was obviously provided by the receptors of the CTL precursor cells with no detectable contribution from the helper-T-cell receptors. Allogeneically activated helper T cells in the responder cell population or in a second irradiated spleen cell population which did not bear the target antigens delivered no substantial helper effect to the CTL precursor cells under test.
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D003208:Concanavalin A / Q000502:physiology*; D003601:Cytotoxicity Tests, Immunologic; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008222:Lymphokines; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000941:Antigens; D008222:Lymphokines; D014301:Trinitrobenzenes; C021649:concanavalin A-induced helper factors; D003208:Concanavalin A