INTERLEUKIN-7 ENHANCES CYTOLYTIC LYMPHOCYTE-T GENERATION AND INDUCES LYMPHOKINE-ACTIVATED KILLER-CELLS FROM HUMAN PERIPHERAL-BLOOD

The effects of purified recombinant interleukin 7 (IL7) on the generation of cytolytic T lymphocytes (CTL) in mixed lymphocyte culture (MLC) and on the induction oflymphokine-activated killer (LAK) cells in autologous cultures of human peripheral blood mononuclear cells were investigated. IL7 was found to induce the generation ofboth CTL and LAK cells in bulk cultures. The appearance of peak CTL activity in MLC established with exogenous IL-7 was delayed in comparison with replicate cultures containing exogenous IL2, but both cytokines stimulated quantitatively similar levels of antigen-specific lytic activity. An IL2-neutralizing antiserum inhibited substantially, but not completely, the effect of IL7 on CTL generation, implying the existence of both an indirect component of 11,7 activity via IL2 utilization, as well as an IL2-independent component. Cell surface phenotypic analysis of 11,2- or IL7-generated CTL effector cells revealed that CD8+ cells were responsible for the vast majority of lytic activity. Limiting dilution analysis (LDA) revealed that essentially identical frequencies of CTL precursors (CTLP) were capable of clonal expansion and/or differentiation in the presence of exogenous IL2, 114, or IL7, supporting the concept that all three of these cytokines are capable of exerting a major influence on T cell growth and differentiation. Approximately half of the CTLP that responded in IL7-supplemented LDA cultures did so in an IL2-independent manner. IL7 stimulated the development of LAK cells in autologous bulk cultures, but only weakly in comparison with IL2. In contrast to its effects on CTL generation, the induction of LAK cells by 11,7 was virtually independent of IL-2. LAK cells induced by IL7, like those induced by 11,2, were phenotypically heterogeneous and included CD8+, CD56+, and γ/δ+ cells. Limiting dilution analysis indicated that 1172 stimulated fivefold more LAK-P than IL7 and 220-fold more than 1174. Collectively, these data suggest that 11,7 has potent regulatory effects on human cytolytic cell populations and, either alone or in combination with other cytokines, could be important for the in vitro expansion of cells for adoptive immunotherapy. © 1990, Rockefeller University Press., All rights reserved.