Article

Intravital mucosal imaging of CD8+ resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory

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Abstract

CD8+ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8+ resident memory T cells (TRM cells) within the reproductive tracts of live female mice. We found that mucosal TRM cells were highly motile, but paused and underwent in situ division after local antigen challenge. TRM cell reactivation triggered the recruitment of recirculating memory T cells that underwent antigen-independent TRM cell differentiation in situ. However, the proliferation of pre-existing TRM cells dominated the local mucosal recall response and contributed most substantially to the boosted secondary TRM cell population. We observed similar results in skin. Thus, TRM cells can autonomously regulate the expansion of local immunosurveillance independently of central memory or proliferation in lymphoid tissue.

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Acknowledgements

We thank the members of the Masopust laboratory for helpful discussions. This work was funded by the Howard Hughes Medical Institute Faculty Scholars program (D.M.) and the US National Institutes of Health (grants R01AI111671 and R01AI084913 to D.M.; grant R21AI123600 to B.J.B.). H.D.H. was funded by the Intramural Research Program of the US National Institute of Allergy and Infectious Diseases.

Author information

Affiliations

  1. Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA

    • Lalit K. Beura
    • , Emily A. Thompson
    • , Jason M. Schenkel
    • , Sathi Wijeyesinghe
    • , Raissa Fonseca
    • , Vaiva Vezys
    •  & David Masopust
  2. Center for Immunology, University of Minnesota, Minneapolis, MN, USA

    • Lalit K. Beura
    • , Jason S. Mitchell
    • , Emily A. Thompson
    • , Jason M. Schenkel
    • , Sathi Wijeyesinghe
    • , Raissa Fonseca
    • , Brandon J. Burbach
    • , Vaiva Vezys
    • , Brian T. Fife
    •  & David Masopust
  3. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    • Jason S. Mitchell
    •  & Brandon J. Burbach
  4. Department of Dermatology, University of Minnesota, Minneapolis, MN, USA

    • Javed Mohammed
  5. Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA

    • Heather D. Hickman
  6. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    • Brian T. Fife

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Contributions

L.K.B., J.S.M., E.A.T., J.M.S., J.M., S.W., R.F. and B.J.B. performed the experiments; H.D.H., V.V. and B.T.F. contributed critical reagents and experimental help; L.K.B., J.S.M. and E.A.T. analyzed intravital microscopy data; L.K.B. and D.M. wrote the manuscript; and D.M. was responsible for research supervision, coordination and strategy.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David Masopust.

Integrated supplementary information

Supplementary information

Videos

  1. Supplementary Video 1

    Migration of CD8+ T cells in the uterine stroma at the peak of viremia

  2. Supplementary Video 2

    Migration of CD8+ T cells at the peak of effector response

  3. Supplementary Video 3

    Migration of resident memory CD8+ T cells in the FRT

  4. Supplementary Video 4

    Reduced migrational speed of TRM cells after local antigen recognition in the FRT

  5. Supplementary Video 5

    Non-antigen-specific recall failed to induce deceleration of TRM cells

  6. Supplementary Video 6

    Cognate antigen interaction is essential for arrest of TRM cell motility in the FRT

  7. Supplementary Video 7

    Examples of memory T cells undergoing division in the uterine stroma

  8. Supplementary Video 8

    TRM cells divide in situ after local reactivation