Expression of IL-17 in human memory CD45RO+ T lymphocytes and its regulation by protein kinase A pathway

In the present study, the authors compared the interleukin 17 (IL-17 expression of human naive and phenotypically defined memory T cells as well as its regulation by cAMP pathway. Our data showed that IL-17 mRNA was highly expressed in memory human peripheral CD8(+) 45RO(+) T cells and CD4(+) 45RO(+) T cells when peripheral blood mononuclear cells were first stimulated with ionomycin/PMA. IL-17 expression in memory CD8(+) T cells required accessory signals since culture of ionomycin/PMA-activated CD8(+) 45RO(+) T cells alone did not result to IL-17 expression. In contrast, memory CD4(+) T cell population seems to be more independent. IL-17 and interferon gamma (IFN-gamma) mRNA were both inhibited in the presence of PGE(2) or the cAMP analogue (dibutyryl-cAMP), while the anti-inflammatory cytokine IL-10 was highly increased, In contrast, naive CD45RA(+) T cells mere unable to express IL-17 whatever the culture conditions, Naive CD4(+) and CD8(+) T cells were sensitive to the PKA regulatory pathway since they represent a significant source of IL-10 when PBMC were first cultured with ionomycin/PMA in the presence of either PGE(2) or db-cAMP. The authors showed that naive cells are highly dependent to their microenvironment, since culture of ionomycin/PMA-activated CD45RA(+) T cells alone did not result in detectable levels of cytokines even in the presence of PGE(2). Results also showed that PGE(2) induced quite the same levels of intracellular cAMP in naive and memory cells suggesting that these cell populations are equally sensitive to PGE,, However, we suggest that PGE(2) may be more efficient in blocking both IL-17 and IFN-gamma expression in already primed memory T cells, rather than in suppressing naive T cells that could represent a significant source of IL-10. Data suggest that PKA activation pathway plays a critical role in the regulation of cytokine profiles and consequently the functional properties of both human naive and memory CD4(+) acid CD8(+) T cells during the immune and inflammatory processes. (C) 1999 Academic Press.