Th1-like Plasmodium-Specific Memory CD4+ T Cells 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, Noah S. Butler

Research output: Contribution to journalArticle

15 Scopus citations

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. Th1 CD4 T cells are widely described as terminally differentiated with a relatively reduced capacity to form memory or support humoral immunity. Using experimental malaria models, Zander et al. show that potent proliferative and B cell helper activity unexpectedly resides within the Plasmodium-specific Th1-like memory CD4 T cell compartment.

Original languageEnglish (US)
Pages (from-to)1839-1852
Number of pages14
JournalCell Reports
Volume21
Issue number7
DOIs
StatePublished - Nov 14 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Zander, R. A., Vijay, R., Pack, A. D., Guthmiller, J. J., Graham, A. C., Lindner, S. E., Vaughan, A. M., Kappe, S. H. I., & Butler, N. S. (2017). Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity. Cell Reports, 21(7), 1839-1852. https://doi.org/10.1016/j.celrep.2017.10.077