A LYMPHOKINE, PROVISIONALLY DESIGNATED INTERLEUKIN-T AND PRODUCED BY A HUMAN ADULT T-CELL LEUKEMIA LINE, STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS

In early phases of human T-cell lymphotropic virus I induced adult T-c ell leukemia (ATL), the malignant cell proliferation is associated wit h an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cell s no longer produce IL-2 yet continue to express high affinity IL-2 re ceptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, th at stimulates T-cell proliferation and the induction of lymphokine-act ivated killer cells. Conditioned medium from HuT-102, when added to th e IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Sinc e CTLL-2 was purported to be IL 2-specific, we performed a number of s tudies to exclude IL-2 production by HuT-102. Stimulation of CTLL-2 ce lls by HuT-102-conditioned medium was not meaningfully inhibited by ad dition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells d id not express mRNA encoding IL-2 as assessed by Northern blot analysi s. No biological activity on CTLL-2 cells was mediated by purified IL- 1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, or g ranulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T i s a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activit y of large granular lymphocytes (i.e., induced lymphokine-activated ki ller cells). Thus, IL-T is a lymphokine that plays a role in T-cell pr oliferation and induction of lymphokine activated killer cells. Furthe rmore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines.