Immunosuppressive factors produced by adult T cell leukemia (ATL) cells and its relation to ATL induction

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Adult T cell leukemia (ATL) is a unique T cell malignancy which is caused by HTLV-i and ATL patients possess severe immunodeficiency. We studied the mechanism of immunodeficiency in ATL patients and character of immunosuppressive factors produced by ATL cells. Sera from ATL patients and the culture supernatant from ATL cells or ATL cell lines suppressed the normal peripheral T cell proliferative responses induced by T cell mitogens. This immunosuppressive factors derived from ATL cells also acted on normal B cells directly and inhibited the proliferation and the differentiation into Ig-producing cells of B cells induced with B cell mitogen. However, the immunosuppressive factors did not affect on the antigen-presentation and IL 1-production of normal macrophages/monocytes. We could not detect the immunosuppressive activity from the sera and the culture suprenatant from peripheral lymphocytes of HTLV-I-carriers. Futhermore, the constitutive expression of CD3 and CD4 on normal T cells was inhibited by the factors. By Sephacryl S-200 column chromatography, the factors were fractionated as a single peak with the molecular weights of 50,000 to 70,000 daltons and their isoelectric point was 4.2 by chromatofocussing techniques. The suppressive activity was unstable to acidtreatment but stable to the treatment woth base, heat, freezing-thawing and trypsin. We are futher studying physiochemical characterization of the suppressive factors by the molecular biological techniques. From these results it can be suggested that the immunodeficiency state in ATL patients is caused by the immunosuppressive factors produced by ATL cells. The immunodeficiency state not only results in various kinds of infections in the host but also provides a more suitable environment for the growth of leukemia cells and leukemogenesis ATL cells.