Interferon‐ γ ‐deficient mice are resistant to the development of alopecia areata

Summary Background  Alopecia areata (AA) is a T‐cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4+ T cells. However, whether T‐helper (Th) 1 or Th2 cytokines are predominant has not yet been defined. Objectives  To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)‐ γ in the experimental induction of AA. Methods  AA was experimentally induced by grafting full‐thickness skin from AA‐affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN‐ γ gene (IFN γ −/− ) and on to wild‐type mice (IFN γ +/+ ). Results  While 90% of wild‐type mice developed AA, none of the IFN γ −/− mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4+ and CD8+ T cells in controls, while in IFN γ −/− mice skin‐infiltrating CD8+ T cells were absent and the number of CD4+ cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune‐privileged infrainfundibular site of the hair follicle was found to be weaker in AA‐resistant IFN γ −/− mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFN γ −/− mice did not respond to the transfer of AA‐affected skin. As distinct from IFN γ +/+ mice, neither T‐cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin‐infiltrating leucocytes of AA‐resistant IFN γ −/− mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFN γ −/− mice. Conclusions  IFN γ −/− mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN‐ γ ‐mediated Th1 activation in the induction of AA.