Glucocorticoids drive human CD8(+) T cell differentiation towards a phenotype with high IL-10 and reduced IL-4, IL-5 and IL-13 production

Glucocorticoids are highly effective in the treatment of allergy and asthma and inhibit the synthesis of IL-4, IL-5 and IL-13 by disease-promoting CD4 (+) Th2 cells. CD8(+) T cells also synthesize these cytokines, and the aim of this study was to investigate how glucocorticoids effect cytokine produc tion by these cells. When CD8(+) T cells are stimulated with anti-CD3 and I L-2 plus IL-4 or dexamethasone, production of the anti-inflammatory cytokin e IL-10 is low in both primary and secondary cultures restimulated with ant i-CDS and IL-2 alone, However, when both are present, a synergistic effect on IL-10 synthesis is observed. The additional presence of antigen-presenti ng cells (APC) in the priming culture maintains IL-10 levels, but inhibits IL-4 and IL-5 production. CD4(+) T cells develop a similar glucocorticoid-i nduced phenotype. These cells demonstrate regulatory activity and inhibit C D4(+) T cell activation in an IL-10-dependent manner. Earlier reports show glucocorticoids promote a Th2 phenotype by effects on purified naive T cell s or pretreatment of APC. This study demonstrates, more critically, that wh en APC are present, glucocorticoids induce CD4 and CD8 T cell populations s ynthesizing high levels of IL-10, but greatly reduced amounts of disease-pr omoting IL-4 and IL-5.