Letter | Published:

Common clonal origin of central and resident memory T cells following skin immunization

Nature Medicine volume 21, pages 647653 (2015) | Download Citation

Abstract

Central memory T (TCM) cells in lymph nodes (LNs) and resident memory T (TRM) cells in peripheral tissues have distinct roles in protective immunity1,2,3,4,5. Both are generated after primary infections, but their clonal origins have been unclear. To address this question, we immunized mice through the skin with a protein antigen, a chemical hapten, or a non-replicating poxvirus. We then analyzed antigen-activated T cells from different tissues using high-throughput sequencing (HTS) of the gene encoding the T cell receptor (TCR) β-chain (Trb, also known as Tcrb) using CDR3 sequences to simultaneously track thousands of unique T cells6. For every abundant TRM cell clone generated in the skin, an abundant TCM cell clone bearing the identical TCR was present in the LNs. Thus, antigen-reactive skin TRM and LN TCM cell clones were derived from a common naive T cell precursor after skin immunization, generating overlapping TCR repertoires. Although they bore the same TCR, TRM cells mediated rapid contact hypersensitivity7 responses, whereas TCM cells mediated delayed and attenuated responses. Studies in human subjects confirmed the generation of skin TRM cells in allergic contact dermatitis. Thus, immunization through skin simultaneously generates skin TRM and LN TCM cells in similar numbers from the same naive T cells.

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Acknowledgements

This work was supported by funding from the US National Institutes of Health (R01 AR065807 to T.S.K., TR01 AI097128 to T.S.K. and R.A.C., R01 AR063962 and R01 AR056720 to R.A.C.). O.G. was supported in part by the Fondation Suisse pour les Bourses en Médecine et Biologie (PASMP3-132622-1).

Author information

Author notes

    • Olivier Gaide

    Present address: Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Affiliations

  1. Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Olivier Gaide
    • , Xiaodong Jiang
    • , Suzanne Nizza
    • , Rachael A Clark
    •  & Thomas S Kupper
  2. Adaptive Biotech, Seattle, Washington, USA.

    • Ryan O Emerson
    •  & Cindy Desmarais
  3. Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.

    • Nicholas Gulati
    •  & James G Krueger
  4. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Harlan Robins

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Contributions

O.G. and T.S.K. conceived and planned the study, reviewed experiments, analyzed data, and wrote the paper. O.G., R.O.E., X.J., N.G. and S.N. performed experiments. H.R., R.O.E., C.D. and J.G.K. helped plan experiments and analyze data, and R.A.C. helped analyze data and edit the paper.

Competing interests

R.O.E. and C.D. have full-time employment and equity ownership at Adaptive Biotechnologies Corporation. H.R. has consultancy, patents and royalties, and equity ownership at Adaptive Biotechnologies Corporation (US patent application number: 20140256567).

Corresponding author

Correspondence to Thomas S Kupper.

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DOI

https://doi.org/10.1038/nm.3860

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