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. 2010 Oct;84(20):10923-7.
doi: 10.1128/JVI.00856-10. Epub 2010 Aug 4.

Mononucleosis and antigen-driven T cell responses have different requirements for interleukin-2 signaling in murine gammaherpesvirus infection

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Mononucleosis and antigen-driven T cell responses have different requirements for interleukin-2 signaling in murine gammaherpesvirus infection

Michael Molloy et al. J Virol. 2010 Oct.

Abstract

Interleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8(+) T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8(+) T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8(+) T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required for CD8(+) T cell mononucleosis.

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Figures

FIG. 1.
FIG. 1.
IL-2 signals are necessary for the optimal expansion of MHV-68-specific CD8+ T cells. WT/CD25−/− chimeric mice were infected with MHV-68 intranasally and bled at set time points. The antigen-specific responses against two dominant epitopes, p79 (A) and p56 (B), were determined via tetramer staining of peripheral blood. p79-specific CD8+ T cells from the WT and CD25−/− populations were stained at the peak of the response (day 14 p.i.) for KLRG1 and CD127 to determine their ability to differentiate into short-lived and memory precursor effector cells (C and D). *, P < 0.05; **, P < 0.01; ***, P < 0.001. Error bars represent standard deviations from the means. Four mice were used per group, and data are representative of at least two experiments.
FIG. 2.
FIG. 2.
CD25−/− CD8+ T cells can respond to secondary challenge. WT/CD25−/− chimeric mice were infected with MHV-68 i.n. After 60 days, the percentage of peripheral blood CD8+ T cells specific for p79 was determined. Mice were then challenged with rVV p79, and the p79+ CD8+ population was determined 5 days postchallenge (A). The numbers in the box represent the averages ± standard deviations. The average fold increase was calculated to determine the ability of WT and CD25−/− CD8+ T cells to respond to a secondary challenge (B). Error bars represent standard deviations from the means. Four mice were used per group, and data are representative of at least two experiments.
FIG. 3.
FIG. 3.
Vβ4+ CD8+ T cells express CD25 upon infection with MHV-68. WT/CD25−/− chimeric mice were infected with MHV-68 i.n., and the percentage of peripheral blood cells that were CD8+ was determined over time for each congenic population (A). Vβ4+ CD8+ T cells from naive and MHV-68-infected mice (day 17 p.i.) were analyzed for expression of CD25 (B and C). Isotype control, filled histogram; naive mice, dashed line; infected mice, solid line (**, P < 0.01). Error bars represent standard deviations from the means. Four mice were used per group, and data are representative of at least two experiments.
FIG. 4.
FIG. 4.
CD8+ T cell-based infectious mononucleosis does not occur in the absence of IL-2 signaling in MHV-68-infected mice. WT/CD25−/− chimeric mice were infected with MHV-68 i.n., and the percentage of Vβ4+ CD8+ T cells was determined over time for each congenic population. Representative plots from day 36 p.i. (A) or the averages over time (B) are shown. WT and CD25−/− CD8+ T cells from chimeric mice were analyzed for expression of CD62L over time. Representative plots from day 24 p.i. (C) or the averages over time (D) are shown. *, P < 0.05; **, P < 0.01). Error bars represent standard deviations from the means. Four mice were used per group, and data are representative of at least two experiments.

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