Loss of interleukin-2 requirement for the generation of T colonies defines an early event of human T-lymphotropic virus type I infection.

ABSTRACT

Accessory cells and/or soluble factors, together with interleukin 2 (IL2), are required for the proliferation and differentiation of phytohemagglutinin (PHA)-activated T lymphocytes. Human T-lymphotropic virus, type I (HTLV-I), a human retrovirus isolated from patients with adult T cell leukemia, can transform T cells in vitro. We investigated the role of HTLV-I-transformed T cell lines as accessory cells in promoting the growth of T colony-forming cells. We found that T cells isolated by E rosetting and then activated with PHA, when seeded with as few as 5 X 10(3) irradiated HTLV-I-producing cells, could generate colonies in the absence of IL2. We analyzed further the effects of HTLV-I virions on T colony formation. Infection of T cells with semipurified HTLV-I viral particles promoted colony formation, in the absence of IL2, of accessory cells or soluble factors. The same results were obtained either with monocyte-depleted T lymphocytes, or with T4 or T8 lymphocytes. Furthermore, T lymphocytes in the presence of heat-inactivated HTLV-I (devoid of replicative potential) could form colonies independently of IL2. Finally, experiments with sera positive for HTLV-I antibodies (to abolish binding of viral particles to cellular receptors) indicated that HTLV-I promoted IL2-independent colony formation, only by "touching" T colony-forming cells. These results taken together demonstrate that the loss of the exogenous IL2 (and other growth-helping factors) requirement defines an early event of HTLV-I infection. The results also suggest that viral attachment to T cells possibly supplies an accessory function triggering autocrine secretion of IL2 by these cells.