HUMAN IL-10 IS A CHEMOATTRACTANT FOR CD8-LYMPHOCYTES AND AN INHIBITOROF IL-8-INDUCED CD4+ T-LYMPHOCYTE MIGRATION( T)

Human IL-10 (hlL-10) is a newly described cytokine that was originally identified as a cytokine synthesis inhibitory factor regulating the p roduction of several pro-inflammatory cytokines such as IL-1alpha, IL- 1beta, IL-6, IL-8, TNF-alpha, and IFN-gamma. Additionally, hIL-10 also inhibits the macrophage-dependent proliferative response of CD4+ T ly mphocytes to Ag stimulation, and it down-regulates the constitutive cl ass II MHC expression on human monocytes. We report hIL-10 to be a pot ent and specific chemotaxin for human T lymphocytes with optimum activ ity in the range between 10 and 100 U/ml. Checkerboard analysis shows the activity to be chemotactic and not chemokinetic. The chemotactic a ctivity is directed toward CD8+ T lymphocytes and not towards CD4+-enr iched cells. Also, hIL-10 lacks chemotactic activity toward human mono cytes or neutrophil granulocytes. Further, we found that hIL-10 inhibi ts the chemotactic response of CD4+, but not CD8+, T cells toward IL-8 . Because hIL-10 can be produced by several cells including CD4+ T cel ls of the Th2 type, our results suggest that hIL-10 participates in a complex regulatory circuit between CD4+ and CD8+ T cells with implicat ions for the control of lymphocyte-mediated inflammatory responses.