T cells in B-cell chronic lymphocytic leukemia: quantitative assessment of cytotoxic and interleukin-2-producing lymphocyte precursors by limiting dilution analysis

Controversy exists as to the functional capacity of T lymphocytes in patients with B-cell chronic lymphocytic leukemia (CLL). We have used a limiting dilution (LD) culture approach to quantitatively assess frequencies of proliferating lymphocyte precursors (PLP), cytotoxic lymphocyte precursors (CLP), and interleukin-2 (IL-2)-producing helper lymphocyte precursors (HLP). Unseparated mononuclear cells (MNC) or purified T cells (E+) and leukemic B cells (E-) were cocultured under LD conditions with irradiated OKT3 hybridoma cells in the absence (determination of HLP) or presence of recombinant IL-2 (determination of PLP and CLP). Under these conditions, low frequencies of PLP, HLP, and CLP (f = 1/65 to 1/4600) were measured in unseparated MNC of CLL patients. In contrast, purified T cells (50% to 92% CD3+) contained precursors of proliferating, IL-2-producing and cytotoxic T cells in similar frequency as did T cells from healthy control donors (f = 1/4 to 1/24). Leukemic B cells rigorously depleted of T cells did not give rise to measurable frequencies of PLP, HLP, or CLP (f less than 1/50.000) except in one CLL patient where a significant frequency (f = 1/1700) of HLP was consistently present in E- cells, despite the absence of growth-inducible PLP and CLP. Taken together, these results indicate that comparable numbers of IL-2-producing helper T cells and cytotoxic T cells are present in B-CLL patients and healthy controls, respectively. The data are discussed with respect to reported T cell abnormalities in B-CLL.