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CD8 T cells require IFNg to induce disease in a murine model of Alopecia Areata 2310132
Abstract   Open access   Peer reviewed

CD8 T cells require IFNg to induce disease in a murine model of Alopecia Areata 2310132

Maddison Lensing, Samuel Connell, Otgonzaya Ayush, Ryan Reis, Zhaowen Zhu, Joan Goverman and Ali Jabbari
The Journal of immunology (1950), Vol.215(Supplement_1), vkag1411694
08/01/2026
DOI: 10.1093/jimmun/vkag141.1694
url
https://doi.org/10.1093/jimmun/vkag141.1694View
Published (Version of record) Open Access

Abstract

Introduction Alopecia Areata (AA) is a prevalent autoimmune disease affecting 2% of the population and presents as nonscarring hair loss. In AA, CD8 T Cells have been found infiltrating around and within the hair follicle and are identified as main drivers of disease. Our transcriptional analysis has revealed that CD8 T cells in the skin of AA patients are poised to make effector molecules such as interferon gamma (IFNg), perforin, and granzymes. Similarly, in the C3H/HeJ murine model of AA, pathogenic NKG2D+ CD8 T cells expressed more IFNg, perforin, and Granzyme B than non-pathogenic T cells. Given the close spatial relationship between CD8 T cells and the hair follicle end target, our objective was to assess the contributions of CD8 T cell-derived molecules during disease. Methods We assessed the role of CD8 T cell molecules in a C3H/HeJ murine model of AA, wherein pathogenic CD8 T cells are sorted from the skin draining lymph nodes of AA mice, expanded in vitro, and intradermally injected into naïve recipients. We used RosaERTcreIFNgKO or RosaERTcrePrfKO mice, capable of tamoxifen-inducible global knockdown of IFNg or Perforin, as donors. Mice globally deficient in the IFNg-receptor(IFNgrKO), bone marrow chimeras with an IFNgrKO hematopoietic compartment, or WT mice were used as recipients. Results We observed perforin deficient CD8 T cells were capable of transferring disease in a manner comparable to WT cells. Conversely, IFNg deficient CD8 T cells failed to transfer disease. Furthermore, global IFNgrKO mice were incapable of developing AA following CD8 T cell induction and bone marrow chimeras containing an IFNgrKO hematopoietic compartment were also unable to develop disease. Conclusion Overall, our findings suggest that perforin is dispensable, while IFNg is a crucial pathogenic effector molecule employed by CD8 T cells in AA. Sensing of IFNg by the immune compartment was a vital step of disease pathogenesis, and future studies may decipher how IFNg sensing by the hair follicle impacts disease.
 Cells - T Cells Diseases - Autoimmunity Molecules - Cytokines Techniques/Approaches - Transgenic/Knockout Mice Tissues - Skin

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