Enhanced expression of human T-cell leukemia/lymphoma virus in neoplastic T cells induced to proliferate by phorbol ester and interleukin-2.

ABSTRACT

Peripheral blood T cells from a patient with T-cell chronic lymphocytic leukemia (T-CLL) failed to respond to mitogenic lectins or alloantigens but could be induced to proliferate by the addition of exogenous interleukin-2 (IL-2). The T-CLL cells also proliferated in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA), or to TPA in combination with phytohemagglutinin (PHA). These TPA-mediated proliferative responses were transient, and only small but significant amounts of IL-2 activity were generated. In contrast, no IL-2 activity was produced after the T-CLL cells had been stimulated with PHA only. The T-CLL cells that were induced to proliferate with PHA and exogenous IL-2 could be maintained in continuous culture by the addition of exogenous IL-2 at regular intervals. These continuously proliferating T-CLL cells failed to produce IL-2 constitutively. However, they could be induced to produce IL-2 activity by stimulation with TPA or TPA plus PHA. Irradiation of the proliferating T-CLL cells prior to incubation with TPA or TPA plus PHA resulted in a 9-fold increase in IL-2 activity, suggesting that the proliferating T-CLL cells were able to consume the IL-2 they produced. Studies on the presence of human T-cell leukemia/lymphoma virus (HTLV) in the fresh and proliferating T-CLL cells revealed that 12% of the fresh cells expressed the HTLV p19 structural core protein. HTLV p19 expression was strongly enhanced in the T-CLL cells induced to proliferate by TPA (66%) and in the continuously growing IL-2-dependent T-CLL cells (82%). In the latter culture, but not in the fresh T-CLL cells, type-C virus particles were observed. These results indicate that HTLV expression correlates with T-CLL cell proliferation but not with IL-2 production by these cells.