PD-1highCXCR5-CD4+peripheral helper T cells promote CXCR3+plasmablasts in human acute viral infection

被引:19
作者
Asashima, Hiromitsu [1 ,2 ]
Mohanty, Subhasis [3 ]
Comi, Michela [1 ,2 ]
Ruff, William E. [1 ,2 ]
Hoehn, Kenneth B. [1 ]
Wong, Patrick [2 ]
Klein, Jon [2 ]
Lucas, Carolina [2 ]
Cohen, Inessa [1 ,2 ]
Coffey, Sarah [1 ,2 ]
Lele, Nikhil [1 ,2 ]
Greta, Leissa [1 ,2 ]
Raddassi, Khadir [1 ,2 ]
Chaudhary, Omkar [3 ]
Unterman, Avraham [5 ]
Emu, Brinda [3 ]
Kleinstein, Steven H. [2 ,4 ,6 ]
Montgomery, Ruth R. [7 ]
Iwasaki, Akiko [2 ,3 ,8 ]
Cruz, Charles S. Dela [5 ]
Kaminski, Naftali [5 ]
Shaw, Albert C. [3 ]
Hafler, David A. [1 ,2 ]
Sumida, Tomokazu S. [1 ]
机构
[1] Yale Sch Med, Dept Neurol, New Haven, CT 06510 USA
[2] Yale Sch Med, Dept Immunobiol, New Haven, CT USA
[3] Yale Univ, Yale Sch Med, Dept Internal Med, Sect Infect Dis, New Haven, CT USA
[4] Yale Sch Med, Dept Pathol, New Haven, CT USA
[5] Yale Univ, Sch Med, Dept Internal Med, Sect Pulm,Crit Care & Sleep Med Sect, New Haven, CT USA
[6] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA
[7] Yale Sch Med, Dept Internal Med, New Haven, CT USA
[8] Howard Hughes Med Inst, Chevy Chase, MD USA
基金
美国国家卫生研究院;
关键词
MEMORY B-CELLS; GERMINAL-CENTERS; VIRUS-INFECTION; IMMUNOGLOBULIN; DIFFERENTIATION; GENERATION; RESPONSES;
D O I
10.1016/j.celrep.2022.111895
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4+ T cell subsets associated with plasma -blast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1highCXCR5-CD4+ T cells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help"signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3 expres-sion, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. Mechanistically, Tph cells help B cell differentiation and produce more interferon g (IFNg), which induces CXCR3 expression on plasmablasts. These results elucidate a role for Tph cells in regulating protective B cell response during acute viral infection.
引用
收藏
页数:19
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