Transcriptional profiling of human V delta 1 T cells reveals a pathogen-driven adaptive differentiation program

McMurray, Jack L.1; von Borstel, Anouk2,3; Taher, Taher E.1; Syrimi, Eleni1,4; Taylor, Graham S.1; Sharif, Maria1; Rossjohn, Jamie2,3,5,6; Remmerswaal, Ester B. M.7; Bemelman, Frederike J.8; Braga, Felipe A. Vieira13; Chen, Xi14; Teichmann, Sarah A.9,10; Mohammed, Fiyaz1; Berry, Andrea A.11; Lyke, Kirsten E.11; Williamson, Kim C.12; Stubbington, Michael J. T.9,15; Davey, Martin S.1,2,3; Willcox, Carrie R.1; Willcox, Benjamin E.1

2022-05-24

10.1016/j.celrep.2022.110858

Cell Reports   影响因子和分区

2211-1247

gamma delta T cells are generally considered innate-like lymphocytes, however, an "adaptive-like" gamma delta compartment has now emerged. To understand transcriptional regulation of adaptive gamma delta T cell immunobiology, we combined single-cell transcriptomics, T cell receptor (TCR)-clonotype assignment, ATAC-seq, and immunophenotyping. We show that adult V delta 1(+) T cells segregate into TCF7(+)LEF1(+)Granzyme B-neg (T-naive) or T-bet(+)Eomes(+)BLIMP-1(+)Granzyme B+ (T-effector) transcriptional subtypes, with clonotypically expanded TCRs detected exclusively in Teffector cells. Transcriptional reprogramming mirrors changes within CD8(+) alpha beta T cells following antigen-specific maturation and involves chromatin remodeling, enhancing cytokine production and cytotoxicity. Consistent with this, in vitro TCR engagement induces comparable BLIMP-1, Eomes, and T-bet expression in naive V delta 1(+) and CD8(+) T cells. Finally, both human cytomegalovirus and Plasmodium falciparum infection in vivo drive adaptive V delta 1 T cell differentiation from T-naive to T-effector transcriptional status, alongside clonotypic expansion. Contrastingly, semi-invariant V gamma 9(+)V delta 2(+) T cells exhibit a distinct "innate-effector" transcriptional program established by early childhood. In summary, adaptive-like gamma delta subsets undergo a pathogen-driven differentiation process analogous to conventional CD8(+) T cells.

SCI

英语

其他

Wellcome Trust Investigator award["099266/Z/12/Z","221725/Z/20/Z"] ; National Institutes of Health (NIH), Division of Allergy and Infectious Diseases (NIAID)["AI-110852","1701447C"] ; NIAID["U01-HD092308","R01-AE141900","AI110820-06"] ; Geneva Foundation[V-12VAXHRFS-03] ; Medical Technology Enterprise Consortium[MTEC-17-01] ; Pfizer["C4591001",1002] ; ARC Discovery Early Career Researcher Award[DE200100292] ; Rebecca L. Cooper Medical Research Foundation[PG2020668] ; ARC Discovery Project[DP210103327]

Cell Biology

Cell Biology

WOS:000805980300003

CELL PRESS

Web of Science

1.Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England
2.Monash Univ, Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic 3800, Australia
3.Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia
4.Birmingham Childrens Hosp, Dept Haematol, Birmingham B4 6NH, W Midlands, England
5.Cardiff Univ, Inst Infect & Immun, Sch Med, Heath Pk, Cardiff CF14 4XN, Wales
6.Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic 3800, Australia
7.Univ Amsterdam, Dept Expt Immunol, Amsterdam Infect & Immun Inst, Amsterdam UMC, Amsterdam, Netherlands
8.Univ Amsterdam, Div Internal Med, Renal Transplant Unit, Amsterdam UMC,Acad Med Ctr, Amsterdam, Netherlands
9.Wellcome Sanger Inst, Cambridge, England
10.European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Cambridge CB10 1SD, England
11.Univ Maryland, Ctr Vaccine Dev & Global Hlth, Sch Med, Baltimore, MD USA
12.Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Hlth Sci, Bethesda, MD USA
13.Amsterdam UMC, Meibergdreef 9, NL-1105 Amsterdam, Netherlands
14.Southern Univ Sci & Technol China, Dept Biol, Shenzhen, Peoples R China
15.10x Genomics Inc, 6230 Stoneridge Mall Rd, Pleasanton, CA 94588 USA

McMurray, Jack L.,von Borstel, Anouk,Taher, Taher E.,et al. Transcriptional profiling of human V delta 1 T cells reveals a pathogen-driven adaptive differentiation program[J]. Cell Reports,2022,39(8).

McMurray, Jack L..,von Borstel, Anouk.,Taher, Taher E..,Syrimi, Eleni.,Taylor, Graham S..,...&Willcox, Benjamin E..(2022).Transcriptional profiling of human V delta 1 T cells reveals a pathogen-driven adaptive differentiation program.Cell Reports,39(8).

McMurray, Jack L.,et al."Transcriptional profiling of human V delta 1 T cells reveals a pathogen-driven adaptive differentiation program".Cell Reports 39.8(2022).