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Th1-like Plasmodium-specific memory CD4+ T cells unexpectedly support humoral immunity
Journal article   Open access   Peer reviewed

Th1-like Plasmodium-specific memory CD4+ T cells unexpectedly support humoral immunity

Ryan A. Zander, Rahul Vijay, Angela D. Pack, Jenna J. Guthmiller, Amy C. Graham, Scott E. Lindner, Ashley M. Vaughan, Stefan H. I. Kappe and Noah S. Butler
Cell reports (Cambridge), Vol.23(4), pp.1230-1237
04/24/2018
DOI: 10.1016/j.celrep.2018.04.048
PMCID: PMC7220064
PMID: 29694898
url
https://doi.org/10.1016/j.celrep.2018.04.048View
Published (Version of record) Open Access

Abstract

Effector T-cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium -specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T-cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium -specific memory CD4 T-cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B-cell help and protection following transfer, characteristics that are enhanced following ligation of the T-cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium -specific memory CD4 T-cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure.

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