Mechanisms of immune privilege in the eye and hair follicle

It has been recognized for over a century that the eye is endowed with remarkable properties that permit the long-term survival of foreign tumor and tissue grafts that are normally rejected at extraocular sites. This ocular immune privilege was originally attributed to a putative sequestration of antigens in the eye as a result of the conspicuous absence of intraocular lymphatic drainage channels. In the last 30 years, a sizeable body of information indicates that ocular immune privilege is a product of multiple anatomical, physiological, and immunoregulatory processes. Ocular tissues and fluids express a wide variety of anti-inflammatory and immunosuppressive molecules, including CD95L (FasL), transforming growth factor-β, macrophage migration inhibitory factor, α-melanocyte-stimulating hormone, calcitonin gene-related peptide, somatostatin, and complement regulatory proteins. Moreover, antigens entering the anterior chamber of the eye evoke a unique form of immune deviation that culminates in the antigen-specific suppression of TH1 immune responses. Finally, the intraocular milieu contains both cell membrane and soluble factors that inhibit both the adaptive and innate immune systems. The hair follicle is also recognized for its immune privilege. Like the anterior chamber of the eye, it produces anti-inflammatory and immunosuppressive cytokines, such as transforming growth factor-β and adrenocorticotrophic hormone. The cells of the hair follicle display limited expression of class Ia MHC molecules and, like cells that line the anterior chamber of the eye, are protected against CD8+ cytotoxic T lymphocyte attack. Gaining a better understanding of the immune privilege of the hair follicle may provide insights into the regulation and pathogenesis of immune-mediated diseases of the skin.