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. Johnson; Afam 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

doi:10.1016/j.cell.2020.11.019

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

Vaccine and Gene Therapy Institute

Research output: Contribution to journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	1946-1961.e15
Journal	Cell
Volume	183
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2020.11.019
State	Published - Dec 23 2020

Keywords

CD8
cytotoxic
lymphatic
recirculation
thoracic duct

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2020.11.019

Cite this

Buggert, M., Vella, L. A., Nguyen, S., Wu, V. H., Chen, Z., Sekine, T., Perez-Potti, A., Maldini, C. R., Manne, S., Darko, S., Ransier, A., Kuri-Cervantes, L., Japp, A. S., Brody, I. B., Ivarsson, M. A., Gorin, J. B., Rivera-Ballesteros, O., Hertwig, L., Antel, J. P., ... Betts, M. R. (2020). The Identity of Human Tissue-Emigrant CD8⁺ T Cells. Cell, 183(7), 1946-1961.e15. https://doi.org/10.1016/j.cell.2020.11.019

Buggert, M, Vella, LA, Nguyen, S, Wu, VH, Chen, Z, Sekine, T, Perez-Potti, A, Maldini, CR, Manne, S, Darko, S, Ransier, A, Kuri-Cervantes, L, Japp, AS, Brody, IB, Ivarsson, MA, Gorin, JB, Rivera-Ballesteros, O, Hertwig, L, Antel, JP, Johnson, ME, Okoye, A , Picker, L, Vahedi, G, Sparrelid, E, Llewellyn-Lacey, S, Gostick, E, Sandberg, JK, Björkström, N, Bar-Or, A, Dori, Y, Naji, A, Canaday, DH, Laufer, TM, Wells, AD, Price, DA, Frank, I, Douek, DC, Wherry, EJ, Itkin, MG & Betts, MR 2020, 'The Identity of Human Tissue-Emigrant CD8⁺ T Cells', Cell, vol. 183, no. 7, pp. 1946-1961.e15. https://doi.org/10.1016/j.cell.2020.11.019

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title = "The Identity of Human Tissue-Emigrant CD8+ T Cells",

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.",

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AU - Buggert, Marcus

AU - Vella, Laura A.

AU - Nguyen, Son

AU - Wu, Vincent H.

AU - Chen, Zeyu

AU - Sekine, Takuya

AU - Perez-Potti, André

AU - Maldini, Colby R.

AU - Manne, Sasikanth

AU - Darko, Samuel

AU - Ransier, Amy

AU - Kuri-Cervantes, Leticia

AU - Japp, Alberto Sada

AU - Brody, Irene Bukh

AU - Ivarsson, Martin A.

AU - Gorin, Jean Baptiste

AU - Rivera-Ballesteros, Olga

AU - Hertwig, Laura

AU - Antel, Jack P.

AU - Johnson, Matthew E.

AU - Okoye, Afam

AU - Picker, Louis

AU - Vahedi, Golnaz

AU - Sparrelid, Ernesto

AU - Llewellyn-Lacey, Sian

AU - Gostick, Emma

AU - Sandberg, Johan K.

AU - Björkström, Niklas

AU - Bar-Or, Amit

AU - Dori, Yoav

AU - Naji, Ali

AU - Canaday, David H.

AU - Laufer, Terri M.

AU - Wells, Andrew D.

AU - Price, David A.

AU - Frank, Ian

AU - Douek, Daniel C.

AU - Wherry, E. John

AU - Itkin, Maxim G.

AU - Betts, Michael R.

PY - 2020/12/23

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N2 - 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.

AB - 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.

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KW - cytotoxic

KW - lymphatic

KW - recirculation

KW - thoracic duct

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