High production of interferon gamma but not interleukin-2 by human T-lymphotropic virus type I-infected peripheral blood mononuclear cells

The transactivator protein of human T-lymphotropic virus I (HTLV-I), Tax, h as been associated with the up-regulation of several host cell genes, inclu ding interleukin 2 (IL-2), the IL-2 receptor-alpha (IL-2R alpha) chain (CD2 5), interferon gamma (IFN-gamma), and tumor necrosis factor (TNF). It has b een proposed that an IL-2/CD25 autocrine loop plays a part in maintaining t he very high proviral loads often found in HTLV-I infection. Furthermore, a bnormal production of inflammatory cytokines might contribute to the pathog enesis of the inflammatory diseases associated with HTLV-I infection. Howev er, there has been no study of the expression of these genes in freshly iso lated peripheral blood mononuclear cells (PBMCs) naturally infected with HT LV-I. In the present study, flow cytometry was used to determine which cyto kines are produced by freshly isolated PBMCs that spontaneously express the HTLV-I Tax protein. Surprisingly, the results show that intracellular Tax expression is associated with rapid up-regulation of IFN-gamma but not TNF or IL-2. A proportion of HTLV-I-infected cells express both IFN-gamma and t he surface markers of effector memory cells. Such cells are capable of migr ation through peripheral tissues and could therefore contribute to the infl ammation seen in diseases such as HTLV-I-associated myelopathy/tropical spa stic paraparesis. (C) 2001 by The American Society of Hematology.