1. Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity
- Author
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Ashley M. Vaughan, Amy C. Graham, Stefan H. I. Kappe, Angela D. Pack, Noah S. Butler, Jenna J. Guthmiller, Rahul Vijay, Ryan Zander, and Scott E. Lindner
- Subjects
0301 basic medicine ,Transgene ,Cell ,Plasmodium ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Receptor ,lcsh:QH301-705.5 ,B cell ,biology ,Effector ,medicine.disease ,biology.organism_classification ,Virology ,Phenotype ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,Immunology ,Humoral immunity ,Malaria ,030215 immunology - Abstract
Summary: 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. Keywords: plasmodium, CD4 T cell, memory, T follicular helper cell, type 1 T helper cell, OX40, T-bet, Bcl-6
- Published
- 2017