Author:
Carpio Victor H.,Aussenac Florentin,Wilson Kyle D.,Villarino Alejandro V.,Dent Alexander L.,Stephens Robin
Abstract
SummaryHybrid Th1/Tfh cells (IFN-γ+IL-21+CXCR5+) predominate in response to persistent infections; however, molecular regulation of their function is poorly defined. In infection withPlasmodium spp, an IFN-γ+T helper-1 (Th1) response controls initial parasitemia, while antibody and IL-21+CXCR5+T follicular helper (Tfh) function effect final clearance. Here, we found that CD4-intrinsic Bcl6, Blimp-1 and STAT3 all regulate T-bet expression, which controls IFN-γ expression. While Bcl6 and Blimp-1 regulate the level of CXCR5, only T-bet and STAT3 affected the functional bias of the Th1/Tfh phenotype. Infected mice with STAT3-deficient T cells produced less antibody, and more IFN-γ+IL-21−CXCR5loT cells, significantly increasing protection from re-infection. Conversely, reduced Th1 bias in re-infected T-bet KO was reflected in prolonged secondary parasitemia. In summary, each feature of hybrid Th1/Tfh population inPlasmodiuminfection is uniquely regulated and the cytokine bias of memory T cells can be modified to enhance the effectiveness of the response.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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