Components of an antigen-/T cell receptorindependent pathway of lymphokine production*
The general way to induce the synthesis of lymphokines by Tcells is the stimulation through theT cell receptor (TcR) complex which results in an increase of intracellular [Ca2+] and in the activation of a tyrosine kinase as well as of protein kinase C. Lymphokine production induced via the TcR is inhibited by the immunosuppressive drug cyclosporin A (CsA). However, an alternative pathway of lymphokine production exists. Several T lymphocyte clones can synthesize interferon-y (IFN-y), granulocyte-monocyte colony-stimulating factor, and small amounts of interleukin (IL 3) when stimulated with syngeneic or allogeneic accessory cells (AC) plus IL 2. In contrast to the TcR pathway the alternative pathway does not require a rise of intracellular [Ca2+] and is insensitive to the effects of CsA. In this report we provide evidence for the involvement of Tcell-stimulating factor (TSF) -a probably novel murine cytokinein the alternative pathway of lymphokine production. It is shown that fixation of the AC with carbodiimide or treatment of the AC with UV light greatly reduces their capacity to induce (in combination with IL 2) the synthesis of IFN-y by Tcells. This function is restored by addition of TSF. Moreover,TSFalone (without IL 2) in combination with fixed AC can induce the synthesis of substantial amounts of IFN-y. Furthermore,TSF in combination with IL 2 can stimulate freshly isolated spleen cells to produce IFN-y. The target cell resides probably in the non-B cell, non-T cell population.