Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection

J Exp Med. 2015 Aug 24;212(9):1405-14. doi: 10.1084/jem.20142101. Epub 2015 Jul 27.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Leishmania major / metabolism*
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / pathology
  • Mice
  • Mice, Transgenic
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Skin / immunology*
  • Skin / parasitology
  • Skin / pathology

Substances

  • Cxcr3 protein, mouse
  • Receptors, CXCR3
  • Interferon-gamma