Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation

Nat Commun. 2016 May 10;7:11514. doi: 10.1038/ncomms11514.


Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4(+) T cells in mouse skin are in equilibrium with the circulation at steady state. These cells are dispersed throughout the inter-follicular regions of the dermis and form clusters with antigen presenting cells around hair follicles. After infection or administration of a contact sensitizing agent, there is a sustained increase in skin CD4(+) T-cell content, which is confined to the clusters, with a concomitant CCL5-dependent increase in CD4(+) T-cell recruitment. Skin CCL5 is derived from CD11b(+) cells and CD8(+) T cells, with the elimination of the latter decreasing CD4(+) T-cell numbers. These results reveal a complex pattern of tissue-retention and equilibration for CD4(+) memory T cells in skin, which is altered by infection and inflammation history.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Aggregation / immunology
  • Cell Movement / immunology
  • Chemokine CCL5 / metabolism
  • Female
  • Hair Follicle / cytology
  • Hair Follicle / immunology
  • Herpes Simplex / immunology
  • Herpes Simplex / pathology
  • Herpesvirus 1, Human
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Middle Aged
  • Skin / cytology
  • Skin / immunology
  • Young Adult


  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Interferon-gamma