Quantitative and functional analysis of a human lymphocyte subset with the T-helper (Leu 3/T 4+) phenotype and natural killer (NK)-cell characteristics in patients with malignancy.

Approximately 20% of normal blood lymphocytes expressing the T-helper (Leu 3/T 4+) surface phenotype display natural killer (NK)-like features such as cytoplasmic granules and the ability to bind NK-cell targets. In this study, we have assessed the frequency, phenotypic features, and functional capabilities of such cells in a variety of lymphoid malignancies or solid tumors. In each patient group, the percentage of granular lymphocytes within the Leu 3/T 4+ T-helper subset was significantly increased. A large percentage of these cells coexpressed the Leu 7 or Leu 15 marker. When Leu 3+ cells from patients with high proportions of such NK-like cells (or Leu 3+-Leu 15+ cells from selected patients) were isolated with a fluorescence-activated cell sorter, these cells did not proliferate in response to allogeneic cells or T-cell mitogens, nor did they provide help for B-cell differentiation. They also did not suppress T-cell proliferative responses or B-cell differentiation. Freshly prepared Leu 3+ granular lymphocytes did not display NK-cell cytotoxic functions. However, after short-term culture in the presence of phytohemagglutinin (PHA), Leu 3+-Leu 15+ cells expressed T-cell growth factor (TCGF) receptors, had a detectable proliferative response to exogenous TCGF, and acquired the ability to lyse NK-cell targets. These studies demonstrate that, in a variety of malignancies, the lymphocyte subpopulation expressing the T-helper (Leu 3/T 4+) phenotype may be comprised largely of cells with NK-like features and functional capabilities distinct from those of classical helper T cells.