052 Identification of Pathogenic T Cell Subsets in Human Alopecia Areata

Alopecia areata (AA) is one of the most common autoimmune diseases, characterized by non-scarring hair loss. The central role of T cells in AA pathogenesis led us to analyze the T cell receptor (TCR) repertoire during the course of AA development. Our previous study of high throughput TCRβ chain sequencing in the mouse model of AA provided evidence for antigenic drive, and showed that pathogenic T cells reside in the CD8+CD103hiNKG2D+ T cell fraction. Here, we performed TCRβ chain sequencing in scalp biopsies and peripheral blood T cell subsets of patchy AA patients and alopecia universalis patients vs. normal controls. Lesional scalp in AA patients showed significantly higher numbers of expanded CD8+ T cell clones than scalp of normal controls. This AA-associated increase in expanded CD8+ scalp T cell clones supports a role for CD8+ T cells in human AA. Further, we identified multiple CD4+ T cell clones that were unique to or present at higher frequencies in lesional compared to non-lesional scalp of the same patient, suggesting an additional role for CD4+ T cells in AA pathogenesis. In contrast to the TCR repertoire of lesional skin in mice that overlapped primarily with NKG2D+CD8+ T cells, expanded lesional CD8+ T cell clones were detected at similar frequencies in both NKG2Dlo and NKG2Dhi CD8+ T cell fractions, suggesting that additional markers are needed to define the pathogenic CD8+ T cells in human AA. Lastly, among the most expanded lesional T cell clones within the same AA patient, we detected near-identical TCRβ chains, and identical TCRβ chains generated by multiple distinct VDJ rearrangements, supporting the notion that human AA is driven by antigen recognition.