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(American Journal of Pathology. 2004;164:623-634.)
© 2004 American Society for Investigative Pathology

Collapse and Restoration of MHC Class-I-Dependent Immune Privilege

Exploiting the Human Hair Follicle as a Model

Taisuke Ito^*, Natsuho Ito^*, Albrecht Bettermann^*, Yoshiki Tokura, Masahiro Takigawa and Ralf Paus^*

From the Department of Dermatology,^* University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany; the Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan; and the Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan

The collapse of major histocompatiblity complex (MHC) class-I-dependent immune privilege can lead to autoimmune disease or fetal rejection. Pragmatic and instructive models are needed to clarify the as yet obscure controls of MHC class I down-regulation in situ, to dissect the principles of immune privilege generation, maintenance, and collapse as well as to develop more effective strategies for immune privilege restoration. Here, we propose that human scalp hair follicles, which are abundantly available and easily studied, are ideally suited for this purpose: interferon- induces ectopic MHC class I expression in the constitutively MHC class-I-negative hair matrix epithelium of organ-cultured anagen hair bulbs, likely via interferon regulatory factor-1, along with up-regulation of the MHC class I pathway molecules ß₂microglobulin and transporter associated with antigen processing (TAP-2). In the first report to identify natural immunomodulators capable of down-regulating MHC class I expression in situ in a normal, neuroectoderm-derived human tissue, we show that ectopic MHC class I expression in human anagen hair bulbs can be normalized by treatment with -MSH, IGF-1, or TGF-ß1, all of which are locally generated, as well as by FK506. These agents are promising candidates for immune privilege restoration and for suppressing MHC class I expression where this is clinically desired (eg, in alopecia areata, multiple sclerosis, autoimmune uveitis, mumps orchitis, and fetal or allograft rejection).

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