Cyclic adenosine monophosphate (cAMP) differentially regulates IL-4 in thymocyte subsets

It was recently reported that cAMP upregulated IL-4 in T cell lines generated in vitro and expressing an unrestricted lymphokine pattern. In order to study the effect of cAMP on IL-4 released by freshly isolated T cell populations, we tested various T cell subsets that have previously been reported to synthesize this lymphokine. We found that cAMP upregulated IL-4 release from in vivo activated single CD4+ peripheral T cells and CD4+CD8-HSAlowNK1.1- thymocytes stimulated with ionomycin and phorbol ester. Furthermore, as in conventional single CD4+ or CD8+ thymocytes, cAMP enhanced IL-4 production in CD4+CD8-NK1.1+ thymocytes. This latter subset has recently been shown to belong to a independent T cell lineage that is positively selected by MHC class I molecules, recognizes CD1 and expresses a restricted T cell receptor repertoire. In contrast, cAMP appeared not to upregulate IL-4 in a third independent T cell lineage. This was suggested by the observation that cAMP did not increase IL-4 in CD3+CD4-CD8- thymocytes, which are thought not to give rise to conventional single CD4+ or CD8+ T cells. It therefore appears that cAMP is coupled differently to IL-4, depending on the T cell lineage. In contrast, in all IL-4 producing stages of conventional T cells, IL-4 is consistently upregulated by cAMP.