Defective T cell responsiveness in chronic lymphocytic leukemia: analysis of activation events

Chronic lymphocytic leukemia (CLL) is a B cell disorder in which major T cell proliferative defects are present. We investigated the nature of this deficit by studying several parameters known to be crucial in normal T cell proliferative response to mitogen. Purified peripheral blood T cells from B-CLL patients were analyzed for the presence of T3 antigen. We observed that CLL T cells have a direct correlation between levels of T3 membrane antigen and proliferative response to mitogen. The appearance of activation antigens (transferrin, HLA-DR, and interleukin 2 [IL 2] receptor) was normal in CLL T cells post-mitogen exposure. Despite the normal presentation of IL 2 receptor on CLL T cell membrane, there was decreased production of IL 2 by CLL patients (v controls) (39.6 +/- 10.2 cells per milliliter v 64.6 +/- 11.0 cells per milliliter). Finally, we were able partially, but not fully, to reconstitute CLL T proliferative response to mitogen by adding purified exogenous IL 2. These findings suggest that CLL T cells have multiple defects that may impact on their proliferative potential. Further insight into these deficits may result in strategies that will facilitate immunologic restoration in T cells of these patients.