Modulation of cytokine responses of murine CD8+alpha beta intestinal intraepithelial lymphocytes by IL-4 and IL-12

The immune responses of the intestine mucosa feature the noninflammatory ty pe, such as IgA production and oral tolerance. Th2 type cytokines have been implicated in the induction of these noninflammatory responses. In the pre sent study, cytokine responses of CD8+ and CD4+ TCR alpha beta+ intestinal intraepithelial lymphocyte (alpha beta iIEL) subsets to TCR stimulation und er the influence of IL-12, IL-4, or CD28 costimulation were examined. IL-12 enhanced production of IL-10 and IFN-gamma by the CD8 alpha beta+ alpha be ta ilEL significantly but only marginally affected the CD8 alpha alpha+ sub set, whereas IL-4 induced IL-4, IL-5, and IL-10 production and augmented TG F-P production by both subsets. CD28 costimulation induced production of Th 2 cytokines by CD4+ ilEL in the absence of exogenous IL-4. Unlike lymph nod e CD4+ cells, the CD28 costimulation-induced Th2 differentiation of CD4+ iI EL was not inhibited by IFN-gamma, These results demonstrate active cytokin e production by CD4+, CD8 alpha beta+, as well as CD8 alpha alpha+ alpha be ta iIEL. The Th2-skewed cytokine profile of CD8 alpha alpha+ alpha beta iIE L and the IFN-gamma-resistance of Th2 differentiation of the CD4+ alpha bet a iIEL suggest that both iIEL subsets contribute to the induction of noninf lammatory mucosal immune responses.