Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells
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journal.ppat.1000815.PDF
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1.51 MB
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Checksum (MD5)
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Author(s)
Wilson, Douglas C.
Grotenbreg, Gijsbert M.
Liu, Kenian
Zhao, Yanlin
Frickel, Eva-Maria
Gubbels, Marc-Jan
Yap, George S.
Ploegh, Hidde
Date Issued
March 2010
Journal
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Citation
Wilson, Douglas C. et al. “Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma Gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells.” Edited by Eric Y. Denkers. PLoS Pathogens 6, 3 (March 2010): e1000815 © 2010 Wilson et al
Version
Final published version
Abstract
Production of the pro-inflammatory cytokine IL-12 by innate phagocytes drives the differentiation of IFN-γ-producing effector T cells during Toxoplasma gondii infection. However, the role of IL-12 in the regulation of memory CD8+ T cell differentiation and function during murine toxoplasmosis is unclear. To track memory CTL development, we identified a novel H-2Kb-restricted CTL population specific for the Toxoplasma antigen tgd057. Tgd057-specific CTLs were induced by both vaccination and natural peroral infection, and were representative of the polyclonal CTL population. Tgd057-specific primary effector cells required IL-12 for the differentiation of KLRG1+ effector subpopulations and IFN-γ production in response to restimulation with parasite-infected cells, but not to restimulation with cognate peptide. The effect of IL-12 deficiency during the primary response was profoundly imprinted on memory CTLs, which continued to show defects in cell numbers, KLRG1+ effector memory subpopulation differentiation, and IFN-γ recall responses. Importantly, isolated CD62Lhi KLRG1- CD8+ T cells differentiated in the absence of IL-12 were enhanced in their ability to generate IFN-γ-producing secondary tgd057-specific effector cells. Our data, for the first time, demonstrate the negative impact of IL-12 signaling on the quality of the central memory CTL compartment. Thus, despite the beneficial role of IL-12 in promoting effector differentiation, excessive exposure to IL-12 during CTL priming may limit the development of long-term protective immunity through the decreased fitness of central memory CTL responses.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Attribution 4.0 International (CC BY 4.0)
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DOI of Published Version
https://doi.org/10.1371/journal.ppat.1000815
