Interleukin 7 stimulates growth of fetal thymic precursors of cytolytic cells: induction of effector function by interleukin 2 and inhibition by interleukin 4

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Abstract
Interleukin 7 (IL-7) and Interleukin 2 (IL-2) stimulate the outgrowth of distinct populations of thymocytes in lobe submersion cultures (LSC) established with day 12−14 murine fetal thymus. Analysis of the expression of cell surface markers in previous studies showed that IL−7 favors the expansion of a more Immature population. In the experiments reported here, populations grown in IL-7 and IL-2 were found to differ functionally as assessed by the expression of cytolytic activity. Whereas cells derived from IL-2-supplemented LSC were highly cytolytic for a broad panel of targets, cells that emerged In IL-7-supplemented cultures exhibited little or no such activity, even in the presence of facilitating lectin. However, there were cells with cytolytic potential present in IL-7-grown populations, as demonstrated by the abrupt appearance of effector function 3 days after their exposure to IL-2. Limiting dilution analysis showed that the absolute number of cells In the cytolytic lineage in fetal thymic lobes Increased during culture in LSC. Interestingly, Identical Increases occurred in IL-7-supplemented and IL-2-supplemented LSC, despite the fact that only the latter population exhibited appreciable lytic activity. Collectively, these results suggest that IL-7 stimulates outgrowth of cell populations which contain functionally inactive cytolytic precursors whose activity is inducible by IL-2. In contrast to IL-2, IL-4 failed to stimulate the appearance of a tytic population from IL-7-supplemented LSC. Furthermore, IL-4 Interfered with cell proliferation and acquisition of lytic activity normally induced by IL-2. These results provide functional evidence that IL-7 stimulates growth of an immature fetal thymocyte whose differentiation can be regulated by IL-2 and IL-4.

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