CD4+ T Follicular Helper Cells in Human Tonsils and Blood Are Clonally Convergent but Divergent from Non-Tfh CD4+ Cells

被引:81
作者
Brenna, Elena [1 ]
Davydov, Alexey N. [2 ]
Ladell, Kristin [3 ]
McLaren, James E. [3 ]
Bonaiuti, Paolo [4 ]
Metsger, Maria [2 ]
Ramsden, James D. [5 ]
Gilbert, Sarah C. [6 ]
Lambe, Teresa [6 ]
Price, David A. [3 ,7 ]
Campion, Suzanne L. [1 ]
Chudakov, Dmitriy M. [2 ,8 ,9 ]
Borrow, Persephone [1 ]
McMichael, Andrew J. [1 ]
机构
[1] Univ Oxford, Nuffield Dept Clin Med, Oxford OX3 7FZ, England
[2] Cent European Inst Technol, Brno 60177, Czech Republic
[3] Cardiff Univ, Sch Med, Div Infect & Immun, Cardiff CF14 4XN, Wales
[4] Ist Firc Oncol Mol, I-20139 Milan, Italy
[5] John Radcliffe Hosp, West Wing ENT, Oxford OX3 9DU, England
[6] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England
[7] Cardiff Univ, Sch Med, Syst Immun Res Inst, Cardiff CF14 4XN, Wales
[8] Pirogov Russian Natl Res Med Univ, Ctr Precis Genome Editing & Genet Technol Biomed, Moscow 117997, Russia
[9] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia
基金
英国医学研究理事会; 美国国家卫生研究院; 英国惠康基金;
关键词
GERMINAL CENTER RESPONSES; CXC CHEMOKINE RECEPTOR-5; B-CELLS; ANTIBODY-RESPONSES; INFLUENZA-VIRUS; HUMAN NAIVE; MEMORY; ANTIGEN; DIFFERENTIATION; INFECTION;
D O I
10.1016/j.celrep.2019.12.016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4(+) T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4(+) cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied.
引用
收藏
页码:137 / +
页数:21
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