HUMAN RECOMBINANT INTERFERON-BETA INFLUENCES T-HELPER SUBSET DIFFERENTIATION BY REGULATING CYTOKINE SECRETION PATTERN AND EXPRESSION OF HOMING RECEPTORS

Type I interferons (IFN) are important regulators of both innate and a cquired immunity. We have used an in vitro system of human CD4(+) T ce ll differentiation to determine how IFN-beta influences development of T helper (Th) subsets and homing receptor expression. IFN-beta promot ed differentiation of CD4(+) T cells that produce low levels of both I FN-gamma, and lymphotoxin compared to interleukin (IL)-12-derived Th1 CD4(+) T cells. IFN-beta inhibited production of Th2 cytokines (IL-5 a nd IL-13) and augmented IL-12-mediated IL-10 secretion. In addition, I FN-beta significantly enhanced L-selectin expression on CD4(+) T cells and synergized with IL-12 to induce expression of cutaneous lymphocyt e-associated antigen (CLA). This Th1 L-selectin(+), CLA(+) phenotype i s characteristic of T cells found in normal human skin and suggests a role for type I IFN in the regulation of Th subset differentiation and tissue-specific homing receptors.