@article{da6c260890de43cfb904cd2ea81fed40,
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.",
keywords = "CD8, cytotoxic, lymphatic, recirculation, thoracic duct",
author = "Marcus Buggert and Vella, {Laura A.} and Son Nguyen and Wu, {Vincent H.} and Zeyu Chen and Takuya Sekine and Andr{\'e} Perez-Potti and Maldini, {Colby R.} and Sasikanth Manne and Samuel Darko and Amy Ransier and Leticia Kuri-Cervantes and Japp, {Alberto Sada} and Brody, {Irene Bukh} and Ivarsson, {Martin A.} and Gorin, {Jean Baptiste} and Olga Rivera-Ballesteros and Laura Hertwig and Antel, {Jack P.} and Johnson, {Matthew E.} and Afam Okoye and Louis Picker and Golnaz Vahedi and Ernesto Sparrelid and Sian Llewellyn-Lacey and Emma Gostick and Sandberg, {Johan K.} and Niklas Bj{\"o}rkstr{\"o}m and Amit Bar-Or and Yoav Dori and Ali Naji and Canaday, {David H.} and Laufer, {Terri M.} and Wells, {Andrew D.} and Price, {David A.} and Ian Frank and Douek, {Daniel C.} and Wherry, {E. John} and Itkin, {Maxim G.} and Betts, {Michael R.}",
note = "Funding Information: We express our gratitude to all donors, health care personnel, study coordinators, administrators, and laboratory managers involved in this work as well as funding agencies. M.B. was supported by the Swedish Research Council, the Karolinska Institutet, the Swedish Society for Medical Research, the Jeansson Stiftelse, the ?ke Wibergs Stiftelse, the Swedish Society of Medicine, the Cancerfonden, the Barncancerfonden, the Magnus Bergvalls Stiftelse, the Lars Hiertas Stiftelse, the Swedish Physician against AIDS Foundation, the Jonas S?derquist Stiftelse, and the Clas Groschinskys Minnesfond. Support was provided by R01 and R56 grants from the National Institutes of Health (AI076066, AI118694, AI106481, UC4 DK112217, P01AI131338, and U19AI149680 to M.R.B. and AI105343, AI117950, AI082630, AI112521, AI115712, AI108545, and CA210944 to E.J.W.) and Stand Up 2 Cancer to E.J.W. Additional support provided to M.R.B. from the Penn Center for AIDS Research (AI045008), and BEAT-HIV Delaney Collaboratory (UM1-AI126620). D.A.P. was supported by a Wellcome Trust Senior Investigator Award (100326/Z/12/Z). E.J.W. is supported by the Parker Institute for Cancer Immunotherapy, which supports the cancer immunology program at UPenn. M.B. and M.R.B. conceived the project; M.B. L.A.V. S.N. Z.C. T.S. A.P.-P. C.R.M. A.R. L.K.-C. A.S.J. I.B.B. M.G.I. and L.H. designed and performed experiments; M.B. L.A.V. S.N. V.W. T.S. A.P.-P. S.M. S.D. J.-B.G. O.R.-B. J.P.A. M.E.J. and G.V. analyzed data; M.B. A.O. L.P. E.S. S.L.-L. E.G. J.S. N.B. A.B.-O. Y.D. A.N. D.H.C. D.A.P. I.F. D.C.D. E.J.W. M.G.I. and M.R.B. provided critical resources; M.B. N.B. D.H.C. T.M.L. A.D.W. D.A.P. D.C.D. E.J.W. and M.R.B. supervised experiments; M.B. and M.R.B. drafted the manuscript; and M.B. D.A.P. and M.R.B. edited the manuscript. The authors declare no competing interests. Funding Information: We express our gratitude to all donors, health care personnel, study coordinators, administrators, and laboratory managers involved in this work as well as funding agencies. M.B. was supported by the Swedish Research Council , the Karolinska Institutet , the Swedish Society for Medical Research , the Jeansson Stiftelse , the {\AA}ke Wibergs Stiftelse , the Swedish Society of Medicine , the Cancerfonden , the Barncancerfonden , the Magnus Bergvalls Stiftelse , the Lars Hiertas Stiftelse , the Swedish Physician against AIDS Foundation , the Jonas S{\"o}derquist Stiftelse , and the Clas Groschinskys Minnesfond . Support was provided by R01 and R56 grants from the National Institutes of Health ( AI076066 , AI118694 , AI106481 , UC4 DK112217 , P01AI131338 , and U19AI149680 to M.R.B. and AI105343 , AI117950 , AI082630 , AI112521 , AI115712 , AI108545 , and CA210944 to E.J.W.) and Stand Up 2 Cancer to E.J.W. Additional support provided to M.R.B. from the Penn Center for AIDS Research ( AI045008 ), and BEAT-HIV Delaney Collaboratory ( UM1-AI126620 ). D.A.P. was supported by a Wellcome Trust Senior Investigator Award ( 100326/Z/12/Z ). E.J.W. is supported by the Parker Institute for Cancer Immunotherapy , which supports the cancer immunology program at UPenn. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = dec,
day = "23",
doi = "10.1016/j.cell.2020.11.019",
language = "English (US)",
volume = "183",
pages = "1946--1961.e15",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}