Cross-linking of T-cell receptors is insufficient to induce IL-2 responsiveness (activation) in resting Lyt-2+ T cells. IL-4 or RIF are essential as second signal.
High-density (resting) murine Lyt-2+ T cells exposed in vitro to the ligand concanavalin A (Con A), or immobilized F23.1 monoclonal antibody (mAb) recognizing an allotypic determinant on the T-cell receptor (TCR), or high-density (resting) allogeneic B stimulator cells remain IL-2-unresponsive; such cells do not express functional IL-2 receptors unless reconstituted with accessory cells. We conclude that cross-linking of TCR is insufficient as signal to induce IL-2 responsiveness, that is, activation. Both the macrophage product RIF and the T-cell product interleukin-4 efficiently induce the IL-2 responsiveness in resting Lyt-2+ T cells exposed in vitro either to the ligand Con A, or to immobilized F23 mAb, or to nonimmunogenic allogeneic stimulator cells. We conclude that two restricting points control the induction of IL-2 responsiveness (activation) in antigen-driven Lyt-2+ T-cell responses, that is, cross-linking of TCR by way of presented antigen and "costimulator" activity expressed by accessory cells. Both RIF and IL-4 express costimulator activity, therefore replacing the requirement for accessory cells.
Wagner
H
H
Department of Medical Microbiology and Immunology, University of Ulm, West Germany.
Heeg
K
K
Hardt
C
C
D000818:Animals; D000950:Antigens, Ly; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015290:Second Messenger Systems; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000950:Antigens, Ly; D016207:Cytokines; D007376:Interleukin-2; D007378:Interleukins; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; C055533:adult T cell leukemia-derived factor; D015847:Interleukin-4