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 acquired immunity. We have used an in vitro system of human CD4(+) T cell differentiation to determine how IFN-beta influences development of T helper (Th) subsets and homing receptor expression. IFN-beta promoted differentiation of CD4(+) T cells that produce low levels of both IFN-gamma, and lymphotoxin compared to interleukin (IL)-12-derived Th1 CD4(+) T cells. IFN-beta inhibited production of Th2 cytokines (IL-5 and IL-13) and augmented IL-12-mediated IL-10 secretion. In addition, IFN-beta significantly enhanced L-selectin expression on CD4(+) T cells and synergized with IL-12 to induce expression of cutaneous lymphocyte-associated antigen (CLA). This Th1 L-selectin(+), CLA(+) phenotype is 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.