The Identity of Human Tissue-Emigrant CD8+ T Cells

Marcus Buggert, Laura A. Vella, Son Nguyen, Vincent H. Wu, Zeyu Chen, Takuya Sekine, André Perez-Potti, Colby R. Maldini, Sasikanth Manne, Samuel Darko, Amy Ransier, Leticia Kuri-Cervantes, Alberto Sada Japp, Irene Bukh Brody, Martin A. Ivarsson, Jean Baptiste Gorin, Olga Rivera-Ballesteros, Laura Hertwig, Jack P. Antel, Matthew E. JohnsonAfam Okoye, Louis Picker, Golnaz Vahedi, Ernesto Sparrelid, Sian Llewellyn-Lacey, Emma Gostick, Johan K. Sandberg, Niklas Björkström, Amit Bar-Or, Yoav Dori, Ali Naji, David H. Canaday, Terri M. Laufer, Andrew D. Wells, David A. Price, Ian Frank, Daniel C. Douek, E. John Wherry, Maxim G. Itkin, Michael R. Betts

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Lymphocyte migration is essential for adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies have been restricted to immunological analyses of blood and various tissues. To address this knowledge gap, we used an integrated approach to characterize tissue-emigrant lineages in thoracic duct lymph (TDL). The most prevalent immune cells in human and non-human primate efferent lymph were T cells. Cytolytic CD8+ T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically skewed and selectively confined to the intravascular circulation, whereas non-cytolytic CD8+ T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Moreover, these anatomically distinct gene expression profiles were recapitulated within individual clonotypes, suggesting parallel differentiation programs independent of the expressed antigen receptor. Our collective dataset provides an atlas of the migratory immune system and defines the nature of tissue-emigrant CD8+ T cells that recirculate via TDL.

Original languageEnglish (US)
Pages (from-to)1946-1961.e15
JournalCell
Volume183
Issue number7
DOIs
StatePublished - Dec 23 2020

Keywords

  • CD8
  • cytotoxic
  • lymphatic
  • recirculation
  • thoracic duct

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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