Oral Infection Drives a Distinct Population of Intestinal Resident Memory CD8(+) T Cells With Enhanced Protective Function

Immunity. 2014 May 15;40(5):747-57. doi: 10.1016/j.immuni.2014.03.007. Epub 2014 May 1.

Abstract

The intestinal mucosa promotes T cell responses that might be beneficial for effective mucosal vaccines. However, intestinal resident memory T (Trm) cell formation and function are poorly understood. We found that oral infection with Listeria monocytogenes induced a robust intestinal CD8 T cell response and blocking effector T cell migration showed that intestinal Trm cells were critical for secondary protection. Intestinal effector CD8 T cells were predominately composed of memory precursor effector cells (MPECs) that rapidly upregulated CD103, which was needed for T cell accumulation in the intestinal epithelium. CD103 expression, rapid MPEC formation, and maintenance in intestinal tissues were dependent on T cell intrinsic transforming growth factor β signals. Moreover, intestinal Trm cells generated after intranasal or intravenous infection were less robust and phenotypically distinct from Trm cells generated after oral infection, demonstrating the critical contribution of infection route for directing the generation of protective intestinal Trm cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adoptive Transfer
  • Animals
  • Antigens, CD / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement / immunology
  • Immunologic Memory / immunology
  • Integrin alpha Chains / biosynthesis
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology*
  • Listeriosis / transmission*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mouth Diseases / microbiology*
  • Transforming Growth Factor beta / immunology

Substances

  • Antigens, CD
  • Integrin alpha Chains
  • Transforming Growth Factor beta
  • alpha E integrins