Interstitial Migration of CD8αβ T Cells in the Small Intestine Is Dynamic and Is Dictated by Environmental Cues

Emily A. Thompson, Jason S. Mitchell, Lalit K. Beura, David J. Torres, Paulus Mrass, Mark J. Pierson, Judy L. Cannon, David Masopust, Brian T. Fife, Vaiva Vezys

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The migratory capacity of adaptive CD8αβ T cells dictates their ability to locate target cells and exert cytotoxicity, which is the basis of immune surveillance for the containment of microbes and disease. The small intestine (SI) is the largest mucosal surface and is a primary site of pathogen entrance. Using two-photon laser scanning microscopy, we found that motility of antigen (Ag)-specific CD8αβ T cells in the SI is dynamic and varies with the environmental milieu. Pathogen-specific CD8αβ T cell movement differed throughout infection, becoming locally confined at memory. Motility was not dependent on CD103 but was influenced by micro-anatomical locations within the SI and by inflammation. CD8 T cells responding to self-protein were initially affected by the presence of self-Ag, but this was altered after complete tolerance induction. These studies identify multiple factors that affect CD8αβ T cell movement in the intestinal mucosa and show the adaptability of CD8αβ T cell motility.

Original languageEnglish (US)
Pages (from-to)2859-2867.e4
JournalCell reports
Volume26
Issue number11
DOIs
StatePublished - Mar 12 2019

Bibliographical note

Funding Information:
We would like to thank Dr. J. Michael Stolley for schematic artistry; Dr. Mark J. Miller for help with SI TPLSM development; Drs. Yoji Shimizu and Brandon Burbach for providing OT-I-GFP mice; and Drs. Stephen Jameson, Kris Hogquist, and Tessa Bergsbaken for sharing Kaede transgenic mice and Yptb-OVA. This work was funded by a University of Minnesota Academic Health Center Seed Grant (to V.V.), NIH grant T32AI007313 (to E.A.T.), and by the University of Minnesota Doctoral Dissertation Fellowship (to E.A.T.). B.T.F. and J.S.M. are supported by NIH R01 AI106791 and P01 AI35296. D.J.T. is supported by NIH UTEP BUILDing SCHOLARS award RL5GM118969 and an NIH Institutional Development Award (IDeA) P20GM1034. D.M. is supported by NIH R01 AI084913.

Funding Information:
We would like to thank Dr. J. Michael Stolley for schematic artistry; Dr. Mark J. Miller for help with SI TPLSM development; Drs. Yoji Shimizu and Brandon Burbach for providing OT-I-GFP mice; and Drs. Stephen Jameson, Kris Hogquist, and Tessa Bergsbaken for sharing Kaede transgenic mice and Yptb-OVA. This work was funded by a University of Minnesota Academic Health Center Seed Grant (to V.V.), NIH grant T32AI007313 (to E.A.T.), and by the University of Minnesota Doctoral Dissertation Fellowship (to E.A.T.). B.T.F. and J.S.M. are supported by NIH R01 AI106791 and P01 AI35296 . D.J.T. is supported by NIH UTEP BUILDing SCHOLARS award RL5GM118969 and an NIH Institutional Development Award (IDeA) P20GM1034 . D.M. is supported by NIH R01 AI084913 .

Publisher Copyright:
© 2019 The Author(s)

Keywords

  • 2-photon microscopy
  • CD8 T cells
  • T cell migration
  • immune surveillance
  • integrins
  • mathematical modeling
  • motility
  • mucosal immunity
  • resident memory T cells
  • tolerance

PubMed: MeSH publication types

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

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