Recognition requirements and regulatory events directing T cell responses

Sammanfattning: The present study has considered cellular and molecular requirements in T cell responses. The central role of T cell growth factors (TCGF) in T cell responses prompted us to study the regulatory events directing TCGF production in lectin stimulated cultures. It was found that normal spleen cells, activated with Concanavalin A for 24 h, develop suppressive cells that block de novo TCGF production by fresh spleen cells. The induction time for effector suppressor cells (nonadherent, Lyt-2-positive T cells) was found to be 18 h and to parallel the termination of TCGF production in situ. The suppressive mechanism is neither iji situ absorption of TCGF produced at control rates nor killing of TCGF producing cells. These results suggest that suppression of TCGF production is an active process which directly and reversibly blocks TCGF-producing cells.This study also indicated that ConA induced a very limited proliferation of Lyt-2- T helper cells (TH) in unselected T cell populations. The activation and growth requirements of Lyt-1+ TH cells were directly investigated and compared with those of Lyt-2+ cytotoxic T lymphocytes (CTL), as defined by the selective expression of Lyt differentiation antigens and functional activities. This analysis revealed a profound difference in activation and growth requirements between these T cell subsets. Thus, while Lyt-2+ CTL precursors can be induced to TCGF reactivity by soluble lectins, in the absence of specialized accessory cells,; Lyt-2" TH cell precursors show a strict accessory cell requirement both for activation and proliteration. Finally, the low level of TH cell effector function, detected in a primary responses to allo-MHC-antigens or lectins, appears to be due to the development of suppressive Lyt2+ T cells.The functional relevance of Lyt-2 antigens expressed on CTL membranes was further assessed in the last part of this study. Two distinct activation systems were used, namely MHC-antigens, provided as UV-irradiated stimulator cells or polyclonal induction by a 4 h pulse, with lectins. Both procedures were shown to selectively induce Lyt-2+ CTL precursors into TCGF reactivity without leading to mitosis, unless TCGF was added. In both cases it was found that monoclonal anti-Lyt-2 antibodies inhibited the two antigen- dependent phases of CTL responses namely, the initial induction step and target cytolysis. The analogy observed between antigen specific and lectin mediated indueton and target cytolysis, with regard to the susceptibility of inhibition by anti-Lyt-2 antibodies has lead to a general hypothesis on CTL activation.