Direct activation of resting T lymphocytes by human T-lymphotropic virus type I

Abstract

The mitogenic or antigenic stimulation of T lymphocytes in the presence of accessory cells results in the synthesis of interleukin-2 (IL-2), which, on interacting with de novo synthesized receptors on the membrane, induces the proliferation and differentiation of T cells. T lymphocytes are the preferential target cells of human T-lymphotropic virus type I (HTLV-I). This virus was isolated from leukaemic cells of patients with adult T-cell leukaemia. No viral transcription was detected in these leukaemic cells, indicating that consistent expression of HTLV-I is not needed for maintenance of the neoplastic state. After a short time in culture, these leukaemic cells produce viral particles which immortalize normal T cells. Hence, HTLV-I might be an important agent not only in the development, but also in the initiation, of this lymphoproliferative disease. This possibility was sustained by our previous observations indicating that normal T lymphocytes incubated with HTLV-I are able to form colonies in soft agar, seven days later, in the absence of exogenous IL-2. These results led us to explore further the immediate effects of viral infection on purified resting T lymphocytes. Here, we present evidence that HTLV-I is able to activate T lymphocytes. Indeed, binding of viral particles to these cells induces IL-2 production and IL-2 receptor expression, and triggers T-cell proliferation. This initial activation, which appears to be independent of accessory cells, may be relevant in understanding the role of HTLV-I in the aetiology of adult T-cell leukaemia.