Journal article
Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity
Cell reports (Cambridge), Vol.21(7), pp.1839-1852
11/14/2017
DOI: 10.1016/j.celrep.2017.10.077
PMID: 29141217
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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•Reagents generated to study Plasmodium-specific memory CD4 T cell development•Th1- and Tfh-like memory CD4 T cells exhibit functional overlap during recall•Potent B cell helper function can be recalled from Th1-like memory cells•Functions of parasite-specific memory CD4 T cells are enhanced by ligation of OX40
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.
Details
- Title: Subtitle
- Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity
- Creators
- Ryan A Zander - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USARahul Vijay - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USAAngela D Pack - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USAJenna J Guthmiller - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAAmy C Graham - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAScott E Lindner - Center for Malaria Research, Penn State University, University Park, PA 16802, USAAshley M Vaughan - Center for Infectious Disease Research, Seattle, WA 98109, USAStefan H.I Kappe - Center for Infectious Disease Research, Seattle, WA 98109, USANoah S Butler - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.21(7), pp.1839-1852
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.celrep.2017.10.077
- PMID
- 29141217
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- DOI: 10.13039/100000060, name: NIH/National Institute of Allergy and Infectious Diseases, award: T32AI007633, K22AI101039, R01AI123341, R01AI125446, R01AI127481; DOI: 10.13039/100000968, name: American Heart Association, award: 16PRE27660002; DOI: 10.13039/100000057, name: NIH/National Institute of General Medical Sciences, award: 8P20GM103447
- Language
- English
- Date published
- 11/14/2017
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001143502771
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