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A Chronic Need for IL-21

Science, 19 June 2009
Vol. 324, Issue 5934, p. 1525-1526
DOI: 10.1126/science.1176487

A Chronic Need for IL-21

  1. Lisa D. S. Johnson and
  2. Stephen C. Jameson
  1. Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  1. E-mail: james024{at}


Chronic viral infections provoke a war of attrition between cytotoxic T cells (the CD8+ subclass) of the immune system and infected host cells. Although the CD8+ T cell response gradually whittles away at the viral load, the cells progressively become “exhausted” and lose function during a chronic infection (1). This exhaustion becomes more severe in the absence of helper CD4+ T cells, potentially leading to viral persistence and loss of virus-specific CD8+ T cells (1, 2). But how do CD4+ cells help? Three reports in this issue, by Elsaesser et al. on page 1569 (3), Yi et al. on page 1572 (4), and Fröhlich et al. on page 1576 (5), suggest an unexpected role for a specific cytokine produced by CD4+ T cells called interleukin-21 (IL-21) in controlling chronic viral infections.


L. D. Johnson and S. C. Jameson, A Chronic Need for IL-21. Science 324, 1525-1526 (2009).

Intratumoral Delivery of IL-21 Overcomes Anti-Her2/Neu Resistance through Shifting Tumor-Associated Macrophages from M2 to M1 Phenotype
M. Xu, M. Liu, X. Du, S. Li, H. Li, X. Li, Y. Li, Y. Wang, Z. Qin, Y.-X. Fu et al.
J. Immunol. 194, 4997-5006 (15 May 2015)

IL-21 Is a Double-Edged Sword in the Systemic Lupus Erythematosus-like Disease of BXSB.Yaa Mice
C. G. McPhee, J. A. Bubier, T. J. Sproule, G. Park, M. P. Steinbuck, W. H. Schott, G. J. Christianson, H. C. Morse, and D. C. Roopenian
J. Immunol. 191, 4581-4588 (1 November 2013)

Children With Islet Autoimmunity and Enterovirus Infection Demonstrate a Distinct Cytokine Profile
W.-C. G. Yeung, A. Al-Shabeeb, C. N. I. Pang, M. R. Wilkins, J. Catteau, N. J. Howard, W. D. Rawlinson, and M. E. Craig
Diabetes 61, 1500-1508 (1 June 2012)

Induction of HLA-DP4-Restricted Anti-Survivin Th1 and Th2 Responses Using an Artificial Antigen-Presenting Cell
M. Tanaka, M. O. Butler, S. Ansen, O. Imataki, A. Berezovskaya, L. M. Nadler, and N. Hirano
Clin. Cancer Res. 17, 5392-5401 (15 August 2011)

Role of antigen persistence and dose for CD4+ T-cell exhaustion and recovery
S. Han, A. Asoyan, H. Rabenstein, N. Nakano, and R. Obst
Proc. Natl. Acad. Sci. USA 107, 20453-20458 (23 November 2010)

IL-21 Deficiency Influences CD8 T Cell Quality and Recall Responses following an Acute Viral Infection
J. S. Yi, J. T. Ingram, and A. J. Zajac
J. Immunol. 185, 4835-4845 (15 October 2010)

T Cell Immunity in Acute HIV-1 Infection
H. Streeck, and D. F. Nixon
The Journal of Infectious Disease 202, S302-S308 (1 October 2010)

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