title: A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.
abstract: Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body.
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore. Electronic address: michael.thomas.wong@merck.com.
authors: Michael Thomas
authors: MT
authors: Wong
authors: Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore 119228, Singapore.
authors: David Eng Hui
authors: DE
authors: Ong
authors: Division of Colorectal Surgery, University Surgical Center, National University Health System, Singapore 119228, Singapore.
authors: Frances Sheau Huei
authors: FS
authors: Lim
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Karen Wei Weng
authors: KW
authors: Teng
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Naomi
authors: N
authors: McGovern
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Sriram
authors: S
authors: Narayanan
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Wen Qi
authors: WQ
authors: Ho
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
authors: Daniela
authors: D
authors: Cerny
authors: Department of Otolaryngology, KK Women's and Children's Hospital, Singapore 229899, Singapore.
authors: Henry Kun Kiaang
authors: HK
authors: Tan
authors: Department of Otolaryngology, KK Women's and Children's Hospital, Singapore 229899, Singapore.
authors: Rosslyn
authors: R
authors: Anicete
authors: Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore 169608, Singapore.
authors: Bien Keem
authors: BK
authors: Tan
authors: Department of Pathology, Singapore General Hospital, Singapore 169856, Singapore.
authors: Tony Kiat Hon
authors: TK
authors: Lim
authors: Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Singapore 169856, Singapore.
authors: Chung Yip
authors: CY
authors: Chan
authors: Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Singapore 169856, Singapore.
authors: Peng Chung
authors: PC
authors: Cheow
authors: Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Singapore 169856, Singapore.
authors: Ser Yee
authors: SY
authors: Lee
authors: Department of Pathology, Singapore General Hospital, Singapore 169856, Singapore.
authors: Angela
authors: A
authors: Takano
authors: Department of Medical Oncology, National Cancer Centre, Singapore 169610, Singapore.
authors: Eng-Huat
authors: EH
authors: Tan
authors: Department of Surgery, National University of Singapore, Singapore 119228, Singapore.
authors: John Kit Chung
authors: JK
authors: Tam
authors: Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore.
authors: Ern Yu
authors: EY
authors: Tan
authors: Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.
authors: Jerry Kok Yen
authors: JK
authors: Chan
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Katja
authors: K
authors: Fink
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore; Emerging Infectious Diseases (EID) Program, Duke-NUS Medical School, Singapore 169857, Singapore.
authors: Antonio
authors: A
authors: Bertoletti
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Florent
authors: F
authors: Ginhoux
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore.
authors: Maria Alicia
authors: MA
authors: Curotto de Lafaille
authors: Agency for Science, Technology and Research (A(∗)STAR), Singapore Immunology Network (SIgN), Singapore 138648, Singapore. Electronic address: evan_newell@immunol.a-star.edu.sg.
authors: Evan William
authors: EW
authors: Newell
mesh_terms: D000818:Animals; D044822:Biodiversity; D015415:Biomarkers / Q000378:metabolism; D001769:Blood / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D009928:Organ Specificity; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016201:Receptors, Lymphocyte Homing