Modulation of IL-2- and IL-4-induced cytotoxicities in human T helper lymphocyte clones by tumor necrosis factor-alpha.
A set of alloreactive IL-2-dependent human CD4+ 45RA-w29+56- Th cell clones was divided into two groups according to their ability to respond to IL-4 by proliferation and their susceptibility to inhibition by TNF-alpha. The latter cytokine blocked proliferative responses to IL-2 of IL-4-nonresponsive clones, but did not affect proliferation of IL-4-responsive clones. In the present communication, it is demonstrated that exposure of apparently non-cytotoxic Th cells to IL-4 resulted in the dose-dependent induction of allospecific CTX in clones previously shown to be capable of responding to IL-4 by proliferation. In contrast, IL-2 induced both allospecific and MHC-unrestricted "NK-like" CTX in both IL-4 responder and nonresponder TCC. However, coculture with IL-4 in addition to IL-2 down-regulated this induction of NK-like CTX by the IL-2 (in those clones capable of responding to IL-4). Acquisition of these two types of CTX by the same TCC was additionally modulated by TNF-alpha, which also blocked the induction of NK-like CTX but had no effect on the induction of allospecific CTX by either IL-2 or IL-4. In contrast, IFN-gamma was unable to block induction of either type of CTX in this model system. These data suggest that even at the clonal level, the relative availability of a number of different up- and down-regulatory cytokines influences the outcome of an immune response. In the present model, IL-2 up-regulates specific and NK-like CTX, the latter component of which is down-regulated by TNF-alpha or IL-4, whereas IL-4 itself can up-regulate specific but not NK-like CTX.
Pawelec
G
G
Second Department of Internal Medicine, University Medical Clinic, Tübingen, Federal Republic of Germany.
D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D006681:HLA-D Antigens; D007376:Interleukin-2; D007519:Isoantigens; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4