Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jun 19;324(5934):1569-72.
doi: 10.1126/science.1174182. Epub 2009 May 7.

IL-21 is required to control chronic viral infection

Heidi Elsaesser  1 , Karsten Sauer, David G Brooks
Affiliations

IL-21 is required to control chronic viral infection

Heidi Elsaesser et al. Science. .

Erratum in

  • Science. 2009 Aug 21;325(5943):946

Abstract

CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection so as to sustain CD8+ T cell responses; however, the necessary factor(s) provided by CD4+ T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrated that interleukin-21 (IL-21) is an essential component of CD4+ T cell help. In the absence of IL-21 signaling, despite elevated CD4+ T cell responses, CD8+ T cell responses are severely impaired. CD8+ T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
IL-21 mRNA expression during viral infection. IL-21 mRNA expression was quantified by real-time reverse transcription polymerase chain reaction after LCMV-Arm or LCMV–Cl 13 infection in (A) uninfected (gray bar), LCMV–Cl 13 infected (black bar), or LCMV–Cl 13 infected and CD4+ T cell–depleted (striped bar) splenocytes or in (B) the indicated sorted cell population. Red Bars indicate cells sorted from LCMV-Arm–infected animals; black bars indicate cells sorted from LCMV–Cl 13–infected animals. (C) Frequency of IFN-γ+ SMARTA T cells that simultaneously produced IL-2 or IL-21 on day 9 and day 30 after infection. Error bars represent the average ± SD of 3 to 5 mice per group and 2 to 4 independent experiments. *P < 0.05, **P = 0.4.
Fig. 2
Fig. 2
IL-21 sustains virus-specific CD8+ T cells during viral persistence. (A) LCMV-GP33–41 MHC class I tetramer staining on days 9 or 30 after LCMV-Arm or LCMV–Cl 13 infection. Numbers indicate the frequency of tetramer+ CD8+ T cells in WT and Il21r−/− (KO) mice. (B) Number of tetramer+ CD8+ T cells on days 9 and 30 after LCMV-Arm or LCMV–Cl 13 infection of WT and Il21r−/− mice. (C) Number of WT or Il21r−/− P14 T cells after infection of Il21r+/+ mice. (D) Frequency of WT and Il21r−/− LCMV-GP33–41 tetramer+ CD8+ T cells in bone-marrow chimeric mice on days 8 and 28 in the blood and on day 28 in the spleen after LCMV–Cl 13 infection. Numbers in parentheses indicate the total proportion of WT and Il21r−/− CD8+ T cells. Bar graphs represent the average ± SD of 3 to 5 mice per group and represent 2 to 4 independent experiments. *P<0.05.
Fig. 3
Fig. 3
IL-21 suppresses CD4+ T cell function. (A) LCMV-GP61–80–specific CD4+ T cell responses on days 9 and 30 after LCMV-Arm or LCMV–Cl 13 infection of WT or Il21r−/− mice. Numbers in each quadrant indicate the frequency of IFN-γ+ and IL-2+ CD4+ T cells and the numbers in parentheses indicate the frequency of IFN-γ and IL-2 double-positive cells. (B) The frequency and number of CD4+ T cells that simultaneously produce IL-2 and IFN-γ on days 9 or 30 after LCMV-Arm or LCMV–Cl 13 infection. (C) Frequency of LCMV-GP61–80 tetramer+ CD4+ T on day 30 after LCMV-Arm or LCMV–Cl 13 infection. The bar graph represents the number of tetramer+ CD4+ T cells. Bar graphs summarize the average ± SD of 3 to 4 mice per group and 3 to 4 independent experiments. *P < 0.05.
Fig. 4
Fig. 4
IL-21 is required to purge chronic viral infection. (A) Serum viral titers after LCMV-Arm (triangles) or LCMV–Cl 13 (circles) infection of WT (black) or Il21r−/− (red) mice. Data are expressed as plaque-forming units (PFU) per milliliter of serum. The dashed line indicates the lower limit of detection (200 PFU/ml). *P < 0.05 for LCMV–Cl 13 infection of WT versus Il21r−/− mice. (B and C) The frequency and number of (B) LCMV-GP33–41 tetramer+ CD8+ T cells and (C) IFN-γ+ CD4+ T cells on day 100 after LCMV–Cl 13 infection of WT and Il21r−/− mice. Time points and bar graphs represent the average ± SD of 3 to 4 mice per group and 3 independent experiments. *P < 0.05.
See this image and copyright information in PMC

Comment in

  • Immunology. A chronic need for IL-21.
    Johnson LD, Jameson SC. Johnson LD, et al. Science. 2009 Jun 19;324(5934):1525-6. doi: 10.1126/science.1176487. Science. 2009. PMID: 19541985 No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zajac AJ, et al. J. Exp. Med. 1998;188:2205. - PMC - PubMed
    1. Gallimore A, et al. J. Exp. Med. 1998;187:1383. - PMC - PubMed
    1. Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. J. Virol. 2003;77:4911. - PMC - PubMed
    1. Brooks DG, Teyton L, Oldstone MB, McGavern DB. J. Virol. 2005;79:10514. - PMC - PubMed
    1. Battegay M, et al. J. Virol. 1994;68:4700. - PMC - PubMed

Publication types