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

11 Citations (Scopus)

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

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Plasmodium
T-cells
Humoral Immunity
T-Lymphocytes
Data storage equipment
Malaria
OX40 Receptor
Parasites
B-Lymphocytes
Theoretical Models
Population
Cells
Th1 Cells
Cytoprotection
Antimalarials
Helper-Inducer T-Lymphocytes
Ligation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zander, R. A., Vijay, R., Pack, A. D., Guthmiller, J. J., Graham, A. C., Lindner, S. E., ... 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
Zander, Ryan A. ; Vijay, Rahul ; Pack, Angela D. ; Guthmiller, Jenna J. ; Graham, Amy C. ; Lindner, Scott E. ; Vaughan, Ashley M. ; Kappe, Stefan H.I. ; Butler, Noah S. / Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity. In: Cell Reports. 2017 ; Vol. 21, No. 7. pp. 1839-1852.
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Zander, RA, Vijay, R, Pack, AD, Guthmiller, JJ, Graham, AC, Lindner, SE, Vaughan, AM, Kappe, SHI & Butler, NS 2017, 'Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity', Cell Reports, vol. 21, no. 7, pp. 1839-1852. https://doi.org/10.1016/j.celrep.2017.10.077

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

In: Cell Reports, Vol. 21, No. 7, 14.11.2017, p. 1839-1852.

Research output: Contribution to journalArticle

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Zander RA, Vijay R, Pack AD, Guthmiller JJ, Graham AC, Lindner SE et al. Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity. Cell Reports. 2017 Nov 14;21(7):1839-1852. https://doi.org/10.1016/j.celrep.2017.10.077