PD-1 Expression Defines Epidermal CD8⁺CD103⁺ T Cells Preferentially Producing IL-17A and Using Skewed TCR Repertoire...

In psoriasis, CD8⁺CD103⁺ memory T cells residing in the epidermis represent an effector population capable of maintaining the condition and driving a recurrence of the disease. Tissue-infiltrating CD8⁺ T cells expressing PD-1 are regarded as antigen-primed effector cells in others chronic inflammatory diseases. However, the expression and significance of PD-1 on skin-infiltrating CD8⁺ T cells in human psoriasis is not known. By analyzing skin-infiltrating T cells from human psoriasis, we found that active psoriatic epidermis contained PD-1 expressing CD8⁺CD103⁺ T cells that correlated with the disease severity and histopathology. PD-1⁺CD8⁺CD103⁺ T cells possessed a canonical psoriasis-specific resident memory phenotype with IL-23R expression and produced IL-17A, whereas PD-1^-CD8⁺CD103⁺ T cells preferentially produced IFN-γ. The diversity of skin-infiltrating T cells was dominated by CD4⁺ T cells, while CD8⁺ T cells, especially CD8⁺CD103⁺T cells, represented an oligoclonal population in active psoriasis. In addition, PD-1⁺CD8⁺CD103⁺T cells used different TCR Vβs from PD-1^-CD8⁺CD103⁺T cells counterpart. In the early resolved lesion, the composition and functional status of PD-1⁺CD8⁺CD103⁺T cells were markedly altered, while PD-1^-CD8⁺CD103⁺ T cells population was minimally changed. Collectively, PD-1 expression delineates a putative pathogenic subset of epidermal CD8⁺CD103⁺ T cells, which possibly play a role in psoriasis pathogenesis.