Human T lymphocyte activation by pokeweed mitogen induces production of TNF-alpha and GM-CSF and helper signaling by IL-1 and IL-6 results in IL-2-dependent T cell growth.
Pokeweed mitogen (PWM) is widely used as an inducer of polyclonal immunoglobulin production, but little attention has been paid to the effects of this lectin on T lymphocytes. In the present study, we analysed the effects of PWM on cytokine production by isolated resting T cells, as well as the involvement of cytokines as accessory signals in PWM-induced T cell activation. The conditions necessary to induce proliferation and production of IL-2, TNF-alpha and GM-CSF by purified T cells, completely depleted of monocytes, B cells and NK cells, could be created by immobilizing PWM through absorption on autologous red blood cells (PWM-RBC), while soluble PWM was totally inactive. IL-4 or IL-6 were not detected in the supernatants. In the presence of PWM-RBC (but not of soluble PWM), T cell proliferation and IL-2 production could strongly and consistently be enhanced by recombinant IL-1 beta and IL-6. On the other hand, the production of TNF-alpha and GM-CSF was not influenced by IL-1 beta and IL-6. Anti-Tac mAb (against the p55 IL-2R) completely inhibited T cell proliferative responses induced by PWM-RBC, thus proving the IL-2-dependency of proliferation. There was no evidence for involvement of IL-4 as a growth factor. In conclusion, PWM directly stimulates human T cells and this results in production of several cytokines including IL-2, GM-CSF and TNF-alpha, and at least one of them (IL-2) is further upregulated by IL-1 beta/IL-6 from accessory cells.
Wallays
G
G
Department of Medicine and Pathophysiology, University of Leuven, Belgium.
Ceuppens
J L
JL
D004912:Erythrocytes; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011043:Pokeweed Mitogens; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor