%0 Journal Article
%T Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection.
%A Eisa M
%A Gomez-Escobar E
%A Bédard N
%A Abdeltawab NF
%A Flores N
%A Mazouz S
%A Fieffé-Bédard A
%A Sakayan P
%A Gridley J
%A Abdel-Hakeem MS
%A Bruneau J
%A Grakoui A
%A Shoukry NH
%J Front Immunol
%V 15
%N 0
%D 2024
%M 38947319
%F 8.786
%R 10.3389/fimmu.2024.1403769
%X <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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).<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.