Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 5, Pages 1264-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2020.10.011
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- National Health and Medical Research Council of Australia [APP1071822]
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HPV16 E7-induced epithelial hyperplasia promotes peripheral Treg expansion in response to intradermal immunization, suppressing antigen-specific CD8+ T-cell responses independently of IL-10. Depletion of these Tregs is not sufficient to restore T helper type 1 immunity.
High-risk human papillomavirus infection can induce cervical and other intraepithelial neoplasia and invasive cancers. A transgenic mouse expressing keratin 14 promotor-driven HPV16 E7 oncoprotein exhibits epithelial hyperplasia and mimics many features of human papillomavirus-related intraepithelial precancers. We have previously demonstrated that HPV16 E7-mediated epithelial hyperplasia suppresses T helper type 1 responses to intradermally delivered antigen and directs differentiation of CD4+ T cells towards a Foxp3+ regulatory phenotype (Treg). Here we establish that Foxp3+ Treg expansion from a transferred naive T-cell population is driven directly by the hyperplastic skin and is independent of pre-existing immune-modulated lymphocytes. However, depletion of endogenous CD25+ Tregs before priming of adoptively transferred T cells significantly improves antigen-specific CD8+T-cell responses but not T helper type 1 responses. Deletion of IL-10 had no effect on Treg expansion, epidermal dendritic cell alteration, and suppression of induced T helper type 1 immunity in HPV16 E7driven hyperplastic mice. Thus, HPV16 E7-mediated epithelial hyperplasia promotes expansion of peripheral Tregs in response to intradermal immunization that suppress antigen-specific CD8+ T-cell responses independently of IL-10, but depletion of these Tregs is not sufficient to restore T helper type 1 immunity.
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