title: Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.
abstract: Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Nelson D
authors.initials: ND
authors.lastname: Glennie
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Venkata A
authors.initials: VA
authors.lastname: Yeramilli
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Beiting
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Volk
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233.
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 pscott@vet.upenn.edu.
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000469:parasitology / Q000473:pathology
chemical_list: C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D007371:Interferon-gamma