IFN-γ and IL-21 Double Producing T Cells Are Bcl6-Independent and Survive into the Memory Phase in Plasmodium chabaudi Infection

Victor H. Carpio, Michael M. Opata, Marelle E. Montañez, Pinaki P. Banerjee, Alexander Dent, Robin Stephens

Research output: Contribution to journalArticle

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Abstract

CD4 T cells are required to fight malaria infection by promoting both phagocytic activity and B cell responses for parasite clearance. In Plasmodium chabaudi infection, one specific CD4 T cell subset generates anti-parasitic IFN-γ and the antibody-promoting cytokine, IL- 21. To determine the lineage of these multifunctional T cells, we followed IFN-γ+ effector T cells (Teff) into the memory phase using Ifng-reporter mice. While Ifng+ Teff expanded, the level of the Th1 lineage-determining transcription factor T-bet only peaked briefly. Ifng+ Teff also co-express ICOS, the B cell area homing molecule CXCR5, and other Tfh lineageassociated molecules including Bcl6, the transcription factor required for germinal center (GC) T follicular helper cells (Tfh) differentiation. Because Bcl6 and T-bet co-localize to the nucleus of Ifng+ Teff, we hypothesized that Bcl6 controls the Tfh-like phenotype of Ifng+ Teff cells in P. chabaudi infection. We first transferred Bcl6-deficient T cells into wildtype hosts. Bcl6-deficient T cells did not develop into GC Tfh, but they still generated CXCR5+IFN-γ+IL- 21+IL-10+ Teff, suggesting that this predominant population is not of the Tfh-lineage. IL-10 deficient mice, which have increased IFN-γ and T-bet expression, demonstrated expansion of both IFN-γ+IL-21+CXCR5+ cells and IFN-γ+ GC Tfh cells, suggesting a Th1 lineage for the former. In the memory phase, all Ifng+ T cells produced IL-21, but only a small percentage of highly proliferative Ifng+ T cells maintained a T-bethi phenotype. In chronic malaria infection, serum IFN-γ correlates with increased protection, and our observation suggests Ifng+ T cells are maintained by cellular division. In summary, we found that Ifng+ T cells are not strictly Tfh derived during malaria infection. T cells provide the host with a survival advantage when facing this well-equipped pathogen, therefore, understanding the lineage of pivotal T cell players will aid in the rational design of an effective malaria vaccine.

Original languageEnglish (US)
Article numbere0144654
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

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Plasmodium chabaudi
T-cells
Malaria
Eragrostis
T-lymphocytes
Eragrostis tef
T-Lymphocytes
Data storage equipment
infection
Helper-Inducer T-Lymphocytes
Germinal Center
cells
malaria
Interleukin-10
interleukin-10
B-lymphocytes
interleukin-21
B-Lymphocytes
Infection
transcription factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

IFN-γ and IL-21 Double Producing T Cells Are Bcl6-Independent and Survive into the Memory Phase in Plasmodium chabaudi Infection. / Carpio, Victor H.; Opata, Michael M.; Montañez, Marelle E.; Banerjee, Pinaki P.; Dent, Alexander; Stephens, Robin.

In: PLoS One, Vol. 10, No. 12, e0144654, 01.12.2015.

Research output: Contribution to journalArticle

Carpio, Victor H. ; Opata, Michael M. ; Montañez, Marelle E. ; Banerjee, Pinaki P. ; Dent, Alexander ; Stephens, Robin. / IFN-γ and IL-21 Double Producing T Cells Are Bcl6-Independent and Survive into the Memory Phase in Plasmodium chabaudi Infection. In: PLoS One. 2015 ; Vol. 10, No. 12.
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