PDF(Pubmed)
Abstract：
UNASSIGNED: Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs.
UNASSIGNED: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8).
UNASSIGNED: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3-) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM-E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6-) subset correlated with the neutralization breadth and potency of NAbs.
UNASSIGNED: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.
UNASSIGNED: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8).
UNASSIGNED: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3-) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM-E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6-) subset correlated with the neutralization breadth and potency of NAbs.
UNASSIGNED: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.
摘要：
■滤泡辅助性T细胞对于在原发性病毒感染期间帮助B细胞的成熟和中和抗体(NAb)的产生是必不可少的。然而,他们在召回响应中的作用尚不清楚。这里,我们使用人类丙型肝炎病毒(HCV)再感染作为模型来研究循环CD4T滤泡辅助细胞(cTfh)和记忆B细胞(MBC)之间的回忆协作相互作用,从而导致NAb的产生.
■我们纵向评估了在随后的再感染事件中自发解决原发性HCV感染的受试者的这种相互作用，该事件导致另一次自发解决（SR/SR，n=14）或慢性感染（SR/CI，n=8）。
■两组都表现出病毒特异性记忆T细胞在再感染时扩增。然而,激活的cTfh（CD4+CXCR5+PD-1+ICOS+FoxP3-）的早期扩增仅发生在SR/SR中。cTfh的激活频率与感染后的时间呈负相关。同时，NAb和HCV特异性MBCs（CD19CD27IgM-E2-Tet）在SR/SR的急性期早期达到峰值，但在SR/CI中未达到峰值。最后,激活的cTfh1（CXCR3CCR6-）子集的频率与NAb的中和宽度和效力相关。
■这些结果强调了早期激活cTfh1细胞在帮助抗原特异性B细胞产生介导HCV再感染清除的NAb中的关键作用。
■我们纵向评估了在随后的再感染事件中自发解决原发性HCV感染的受试者的这种相互作用，该事件导致另一次自发解决（SR/SR，n=14）或慢性感染（SR/CI，n=8）。
■两组都表现出病毒特异性记忆T细胞在再感染时扩增。然而,激活的cTfh（CD4+CXCR5+PD-1+ICOS+FoxP3-）的早期扩增仅发生在SR/SR中。cTfh的激活频率与感染后的时间呈负相关。同时，NAb和HCV特异性MBCs（CD19CD27IgM-E2-Tet）在SR/SR的急性期早期达到峰值，但在SR/CI中未达到峰值。最后,激活的cTfh1（CXCR3CCR6-）子集的频率与NAb的中和宽度和效力相关。
■这些结果强调了早期激活cTfh1细胞在帮助抗原特异性B细胞产生介导HCV再感染清除的NAb中的关键作用。
