Multimodally profiling memory T cells from a tuberculosis cohort identifies cell state associations with demographics, environment and disease
Nathan, Aparna; Beynor, Jessica I; Baglaenko, Yuriy; Suliman, Sara; Ishigaki, Kazuyoshi; Asgari, Samira; Huang, Chuan-Chin; Luo, Yang; Zhang, Zibiao; Lopez, Kattya; Lindestam Arlehamn, Cecilia S; Ernst, Joel D; Jimenez, Judith; Calderón, Roger I; Lecca, Leonid; Van Rhijn, Ildiko; Moody, D Branch; Murray, Megan B; Raychaudhuri, Soumya
(2021) Nature Immunology, volume 22, issue 6, pp. 781 - 793
(Article)
Abstract
Multimodal T cell profiling can enable more precise characterization of elusive cell states underlying disease. Here, we integrated single-cell RNA and surface protein data from 500,089 memory T cells to define 31 cell states from 259 individuals in a Peruvian tuberculosis (TB) progression cohort. At immune steady state >4 years
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after infection and disease resolution, we found that, after accounting for significant effects of age, sex, season and genetic ancestry on T cell composition, a polyfunctional type 17 helper T (TH17) cell-like effector state was reduced in abundance and function in individuals who previously progressed from Mycobacterium tuberculosis (M.tb) infection to active TB disease. These cells are capable of responding to M.tb peptides. Deconvoluting this state-uniquely identifiable with multimodal analysis-from public data demonstrated that its depletion may precede and persist beyond active disease. Our study demonstrates the power of integrative multimodal single-cell profiling to define cell states relevant to disease and other traits.
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Keywords: Immunology and Allergy, Immunology
ISSN: 1529-2908
Publisher: Nature Publishing Group
Note: Funding Information: We thank K. Slowikowski for building an interactive data browser. This work is supported in part by funding from the National Institutes of Health (U19 AI111224 to S.R., M.B.M. and D.B.M.; UH2AR067677 to S.R.; T32 HG002295 to A.N.; T32 AR007530 to A.N.; U01 HG009379 to S.R.; U19 AI111211 to J.D.E.; and R01AI049313 to D.B.M.). Publisher Copyright: © 2021, Springer Nature America, Inc.
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