Luster, Andrew/0000-0001-9679-7912; Chasse, Alexandra/0000-0001-7970-2053WOS: 000565154100003PubMed: 32877667CD8(+) tissue-resident memory T cells (T-RM) persist at sites of previous infection, where they provide rapid local protection against pathogen challenge. CD8(+) T-RM expressing the alpha 1 chain (CD49a) of integrin VLA-1 have been identified within sites of resolved skin infection and in vitiligo lesions. We demonstrate that CD49a is expressed early following T cell activation in vivo, and TGF-beta and IL-12 induce CD49a expression by CD8(+ )T cells in vitro. Despite this rapid expression, CD49a is not required for the generation of a primary CD8(+) T cell response to cutaneous herpes simplex virus (HSV) infection, migration of CD8(+) T cells across the epidermal basement membrane, or positioning of T-RM within basal epidermis. Rather, CD49a supports CD8(+) T-RM persistence within skin, regulates epidermal CD8(+) T-RM dendritic extensions, and increases the frequency of IFN-gamma(+) CD8(+) T-RM following local antigen challenge. Our results suggest that CD49a promotes optimal cutaneous CD8(+) T-RM-mediated immunity.NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 AI121546]; [HSV-1 gB 498-505 SSIEFARL]We would like to thank Dr. David Topham for providing Itga1-/- mice, Dr. David Knipe for providing HSV-KOS and advice on working with HSV, and Dr. Thomas Gebhardt for providing HSV-OVA. the following reagent was obtained through the NIH TetramerCore Facility: H-2K(b) HSV-1 gB 498-505 SSIEFARL. the graphical abstract was produced using BioRender. This work was supported by NIH grant R01 AI121546 (to S.K.B.)
