(109) Prior antigen experience influences the development of alopecia areata in C3H/HeJ mice

Introduction/Rationale: Alopecia areata (AA) is an autoimmune disease of the hair follicle (HF) with a 2% lifetime incidence, characterized by well-defined patches of hair loss on the scalp. AA arises from the breakdown of HF immune privilege, leading to T cell infiltration and attack of the HF. Unlike humans who are continually exposed to diverse microbes, laboratory mice are maintained under specific pathogen–free (SPF) conditions, limiting their immune experience. Recent studies have shown that pet-store mice more closely replicate human immune responses. C3H/HeJ (C3H) mice are a common model to study AA and can be induced using skin grafts from affected mice; however, these mice are typically maintained in SPF facilities. This study aimed to determine whether immunologically experienced C3H mice, induced to develop AA, would harbor a skin environment that more closely mimics human patients.

Methods: To test this, we generated mice using a sequential infection model, replicating findings in pet-store mice, by infecting C3H mice with influenza A virus, vaccinia virus, Listeria monocytogenes, and lymphocytic choriomeningitis virus Armstrong at 5-day intervals.

Results: Sequentially infected mice, before disease induction, exhibited increased frequencies of antigen-experienced CD8 T cells in blood and skin-draining lymph nodes (SDLNs) compared to non-infected mice. They also showed elevated NKG2D⁺ CD8 T cells, a population known to drive AA. We hypothesized that AA onset would be accelerated following skin-graft induction. Surprisingly, previously infected mice developed AA at a reduced rate and exhibited fewer AA-associated T cells in SDLNs and skin compared to controls.

Conclusion: Ongoing studies will determine whether sequential infections alter precursor frequency of autoimmune T cells. Together, these data suggest that prior microbial exposure reshapes the immune landscape in C3H mice, attenuating AA-specific immune responses and supporting future studies to dissect how infections influence AA development.