IFN-y And IL-21 Double Producing T Cells Are Bcl6-Independent And Survive Into The Memory Phase In Plasmodium chabaudi Infection

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dr.. Michael Opata, Assistant Professor (Creator)
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

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-y and the antibody-promoting cytokine, IL-21. To determine the lineage of these multifunctional T cells, we followed IFN-y+ effector Tcells (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 lineage-associated 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 wild type hosts. Bcl6-deficient T cells did not develop into GC Tfh, but they still generated CXCR5 + IFN-y+IL-21+IL-10 + Teff, suggesting that this predominant population is not of the Tfh-lineage. IL-10 deficient mice, which have increased IFN-y and T-bet expression, demonstrated expansion of both IFN-y+IL-21 +CXCR5 + cells and IFN-y+ 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-bet hi phenotype. In chronic malaria infection, serum IFN-y 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.

Additional Information

Carpio VH, Opata MM, MontaƱez ME, Banerjee PP, Dent AL, Stephens R (2015) IFN-? and IL-21 Double Producing T Cells Are Bcl6-Independent and Survive into the Memory Phase in Plasmodium chabaudi Infection. PLoS ONE 10(12): e0144654. doi:10.1371/journal.pone.0144654. Publisher version of record available at: https://doi.org/10.1371/journal.pone.0144654
Language: English
Date: 2015
T cells, Malaria, T helper cells, Cytokines

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