5 years ago

Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity

Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity
Ashley M. Vaughan, Scott E. Lindner, Stefan H.I. Kappe, Amy C. Graham, Angela D. Pack, Jenna J. Guthmiller, Noah S. Butler, Ryan A. Zander, Rahul Vijay


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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31540-1

DOI: 10.1016/j.celrep.2017.10.077

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