Cross‐sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation

Summary

Background

Cutaneous viral infections and immune suppression are risk factors for some forms of non‐melanoma skin cancer (NMSC), however, their interrelationship is poorly understood. Objective: To examine cross‐sectional associations between cutaneous viral infections and circulating forkhead‐box P3 (FOXP3) expressing T regulatory (Treg) cells, suppressive cells that dampen effective anti‐tumour immunity.

Methods

Blood, eyebrow hair (EBH) and skin swab samples (SSW) were collected from 352 skin screening patients 60 years and older without prevalent skin cancer participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4^high Treg cells, both previously associated with cutaneous diseases. Age‐ and gender‐adjusted associations between circulating T‐cell populations and infection were estimated using logistic regression.

Results

Total Treg cell proportion in peripheral blood was not associated with beta HPV or HPyV infection. However, the proportion of circulating CLA⁺ Treg cells was inversely associated with gamma HPV EB infection (OR= 0·54, 95% CI=0·35‐0·84). Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27^‐CD45RA^‐FOXP3⁺CD4⁺) were also inversely associated with gamma HPV infection in SS (OR=0·55, 95% CI=0·30‐0·99) and EB (OR=0·56, 95% CI=0·36‐0·86).

Conclusions

Inverse associations between circulating Treg cells and gamma HPV infection suggest that localised viral infection may promote immunosuppressive cell migration into skin.

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