Circulating memory CD8+ T cells are limited in forming CD103+ tissue-resident memory T cells at mucosal sites after reinfection

Eur J Immunol. 2021 Jan;51(1):151-166. doi: 10.1002/eji.202048737. Epub 2020 Aug 31.

Abstract

Tissue-resident memory CD8+ T cells (TRM ) localize to barrier tissues and mediate local protection against reinvading pathogens. Circulating central memory (TCM ) and effector memory CD8+ T cells (TEM ) also contribute to tissue recall responses, but their potential to form mucosal TRM remains unclear. Here, we employed adoptive transfer and lymphocytic choriomeningitis virus reinfection models to specifically assess secondary responses of TCM and TEM at mucosal sites. Donor TCM and TEM exhibited robust systemic recall responses, but only limited accumulation in the small intestine, consistent with reduced expression of tissue-homing and -retention molecules. Murine and human circulating memory T cells also exhibited limited CD103 upregulation following TGF-β stimulation. Upon pathogen clearance, TCM and TEM readily gave rise to secondary TEM . TCM also formed secondary central memory in lymphoid tissues and TRM in internal tissues, for example, the liver. Both TCM and TEM failed to substantially contribute to resident mucosal memory in the small intestine, while activated intestinal TRM , but not liver TRM , efficiently reformed CD103+ TRM . Our findings demonstrate that circulating TCM and TEM are limited in generating mucosal TRM upon reinfection. This may pose important implications on cell therapy and vaccination strategies employing memory CD8+ T cells for protection at mucosal sites.

Keywords: CD103+ CD8+ T cells; CD8+ T cells; LCMV; memory CD8+ T cells; tissue-resident T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adoptive Transfer
  • Animals
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes / classification
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Female
  • Humans
  • Immunity, Mucosal*
  • Immunologic Memory*
  • Integrin alpha Chains / immunology*
  • Integrin alpha Chains / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestine, Small / cytology
  • Intestine, Small / immunology
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Transforming Growth Factor beta / immunology

Substances

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