IL-4 induces IL-2 receptor p75 beta-chain gene expression and IL-2-dependent proliferation in mouse T lymphocytes.
T and B cells exhibit complex responses to the combination of IL-2 and IL-4, each of which can act as a growth or differentiation factor for lymphocytes under certain circumstances. To characterize better the mechanism by which these cytokines interact, mRNA levels of the signal-transducing p75 beta-chain of the IL-2R were analyzed. These studies show that IL-4 increases expression of the IL-2R beta-chain in mouse splenic B and T cells, and the response of B cells was potentiated by concurrent cross-linking of surface Ig. Kinetic analysis of the IL-2R beta response showed a slow onset but maintenance of peak levels of expression between 10 and 24 h. These data indicate that the pathways involved in the lymphocyte response to IL-4 differ for IL-2R and IL-4R, and that the induction of IL-4R precedes the increase in IL-2R. The effect of IL-4 on IL-2R beta mRNA levels was mediated in part by an increase in the rate of gene transcription, and was associated with increased IL-2 binding in the absence of any change in IL-2R alpha levels. In addition, IL-4 increased the level of IL-2R beta expression in thymocytes. Proliferation assays demonstrated that pretreatment of splenic T cells with IL-4 led to a substantial increase in IL-2-dependent proliferation. These results are consistent with a mechanism by which IL-4 can prime T cells and certain thymocytes for responsiveness to IL-2 by increasing IL-2R p75 chain gene expression, independent of general T cell activation.
Casey
L S
LS
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Lichtman
A H
AH
Boothby
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4