MHC CLASS-I EXPRESSION IN MURINE SKIN - DEVELOPMENTALLY CONTROLLED AND STRIKINGLY RESTRICTED INTRAEPITHELIAL EXPRESSION DURING HAIR FOLLICLE MORPHOGENESIS AND CYCLING, AND RESPONSE TO CYTOKINE TREATMENT IN-VIVO

Hair bulb keratinocytes generate one of the few ''immune privileged'' tissue compartments of the mammalian organism by suppressing classical MHC class I (MHC Ia) antigens, Expression of non-classical MHC class I(MHC Ib) antigens in the follicle has been found, but only in its dis tal epithelium. Here, we have defined when during murine hair follicle morphogenesis these peculiar MHC Ia and Ib expression patterns are es tablished, how they change during the murine hair cycle, and how diffe rent MHC I modulatory agents alter follicular MHC Ia and Ib expression in vivo. During neonatal hair follicle morphogenesis in C57BL/6 mice, distal follicle keratinocytes began to express MHC Ia (H2(b)) only la te in development. The MHC Ib antigens, Qa-l and Qa-2, did not become visible until the initiation of follicle cycling, with Qa-l expression being more widespread than that of Qa-2. H2(b), Qa-1, and TAP-1 immun oreactivity on previously negative keratinocytes of the proximal anage n hair bulb was upregulated by intradermal injection of the proinflamm atory cytokine interferon-gamma, but not by tumor necrosis factor-alph a or interleukin-1 beta, Injection of the reportedly MHC class I downr egulating agents interleukin-10, insulin-like growth factor-1, transfo rming growth factor-beta, alpha-melanocyte stimulating hormone, or dex amethasone, however, all failed to downregulate constitutive or interf eron-gamma-induced follicular MHC Ia expression. This shows that the h air follicle is a previously unrecognized site of Qa-1 expression and that interferon-gamma is a key regulator of follicular MHC I expressio n in vivo. It also suggests that the developmental and immunologic con trols of MHC I expression by follicle keratinocytes differ from those of other epithelial cells.