CD4+ T cells inhibit the generation of CD8+ epidermal-resident memory T cells directed against clinically relevant contact allergens

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Background: CD8+ epidermal-resident memory T (TRM) cells play central roles in local flare-up responses to experimental contact allergens by inducing massive influx of neutrophils to the epidermis upon allergen challenge. Whether similar immunopathogenic mechanisms are involved in the responses to clinically relevant contact allergens is unknown. Methods: The immune response to cinnamal, ρ-phenylenediamine (PPD) and methylisothiazolinone (MI) was studied in a well-established mouse model for allergic contact dermatitis that includes formation of TRM cells by ELISA, flow cytometry, fluorescence microscopy analyses and cell depletion protocols. Results: We show that the formation of CD4+ and CD8+ epidermal TRM cells and the inflammatory response are highly allergen-dependent. However, the magnitude of the flare-up responses correlated with the number of epidermal CD8+ TRM cells, CXCL1/CXCL2 release and recruitment of neutrophils to the epidermis. Finally, depletion of CD4+ T cells strongly enhanced the number of epidermal CD8+ TRM cells, the flare-up response and the epidermal infiltration of neutrophils for all allergens. Conclusion: As the first, this study demonstrates that clinically relevant contact allergens have the ability to generate pathogenic, epidermal CD8+ TRM cells that recruit neutrophils following re-exposure to the allergen, but that this normally is counteracted by the simultaneous induction of anti-inflammatory CD4+ T cells.

TidsskriftContact Dermatitis
Udgave nummer6
Sider (fra-til)425-437
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work is supported by the LEO Foundation, the Danish Research Council and the A.P. Møller Foundation for the Advancement of Medical Science and the Danish Environmental Protection Agency as part of the Chemicals Act. The study was performed as part of the collaboration in the Clinical Academic Group Allergy, Copenhagen Health Science Partners.

Publisher Copyright:
© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.

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