Acquisition of suppressive activity and natural killer-like cytotoxicity by human alloproliferative "helper" T cell clones.

To investigate potential functional changes in alloantigen-specific proliferative CD3+, CD4+, CD8-, Leu-8-, interleukin 2 (IL 2)-secreting noncytotoxic in vitro primed human helper T cells, a set of 12 clones was studied sequentially throughout their finite life spans. Clones surviving to greater than 30 population doublings (PD) retained their requirements for exogenous IL 2 and filler cells for continued growth, but lost the ability to proliferate and to secrete IL 2 when specifically restimulated. This was not accompanied by changed surface marker phenotypes or acquisition of abnormal karyotypes, but was accompanied by the acquisition of MHC-unrestricted potent radioresistant suppressive activity for lympho-proliferative responses. Suppression was not caused by absorption of IL 2, secretion of interferons, de novo mycoplasma contamination, or cytotoxic activity. At least two suppressive mechanisms were demonstrated: 1) the induction of suppressor effectors in naive lymphocyte populations, which required cell to cell contact and could be inhibited by certain monoclonal antibodies against MHC class II determinants; and 2) a direct effect on responding lymphocytes, shown by suppressive activity on cloned PLT-active reagents. Moreover, the majority (75%) of originally allo-proliferative clones also acquired a previously absent cytotoxicity against natural killer (NK) cell-susceptible, but not NK-resistant, target cell lines. This modulation of function from specific alloproliferative, IL 2-secreting nonsuppressive status to strong nonspecific suppressive and NK-like cytotoxic status represents a novel functional activity of human T helper lymphocytes under conditions of clonal propagation.