Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes

Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We fo und that not only IFN-induced but also normal basal expression of MHC I req uired IFN receptors and signal transducer and activator of transcription (S TAT)1, providing genetic evidence for continuous IFN signaling. Surprisingl y, an IFN-independent requirement for STAT1 was also found, specifically in T lymphocytes, where MHC class I expression was not fully accounted for by IFN signaling. This IFN-independent pathway maintained tyrosine phosphoryl ation of STAT1 in T but not B lymphocytes even in the absence of IFN recept ors. Interestingly, interleukin (IL)-7 selectively activated STAT1 and indu ced MHC class I in mature T but not B cells. These loss of function studies demonstrate an essential role of endogenous IFN and activated STAT1 for co nstitutive MHC class I expression in normal mice and define IL-7-dependent but IFN-independent regulation of STAT1 restricted to T lymphocytes.