Interleukin 7 stimulates growth of fetal thymic precursors of cytolytic cells: induction of effector function by interleukin 2 and inhibition by interleukin 4.
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 lytic population from IL-7-supplemented LSC. Furthermore, IL-4 interfered with cell proliferation and acquisition of lytic activity normally induced by IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Widmer
M B
MB
Immunex Corporation, Seattle, WA 98101.
Morrissey
P J
PJ
Namen
A E
AE
Voice
R F
RF
Watson
J D
JD
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D005333:Fetus / Q000166:cytology / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology
D007376:Interleukin-2; D015851:Interleukin-7; D015847:Interleukin-4