Epidermal T cell subsets—Effect of age and antigen exposure in humans and mice

Background: Epidermal T cells play a central role in immune surveillance and in inflammatory skin diseases. Major differences in the epidermal T cell composition are found between adult humans and antigen-inexperienced laboratory mice. Whether this is due to inborn species differences, to different environmental exposures, or a combination of the two is a matter of debate. Objectives: To investigate the role of age and exposure to antigens on epidermal T cell subsets in human and mouse skin. Methods: We isolated T cells from the epidermis from 19 infants and 26 adults, and determined the frequency of CD4⁺ and CD8⁺ αβ T cells and γδ T cells by flow cytometry. In addition, we determined the epidermal T cell composition in antigen-inexperienced and antigen-experienced mice. Results: We found that humans are born with very few epidermal T cells. The number increases and the composition changes with age. In antigen-inexperienced mice, the epidermal T cell composition is unaffected by age, but it is dramatically affected by antigen exposure. Conclusion: Taken together, we show that antigen exposure, as opposed to age, is the major factor determining the composition of epidermal T cells, suggesting that the skin of antigen-experienced mice better reflects the immunological conditions in human skin.