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Science 334 (6057): 825-829

Copyright © 2011 by the American Association for the Advancement of Science

Late Interleukin-6 Escalates T Follicular Helper Cell Responses and Controls a Chronic Viral Infection

James A. Harker,1 Gavin M. Lewis,1 Lauren Mack,1 Elina I. Zuniga1,*

Abstract: Multiple inhibitory molecules create a profoundly immunuosuppressive environment during chronic viral infections in humans and mice. Therefore, eliciting effective immunity in this context represents a challenge. Here, we report that during a murine chronic viral infection, interleukin-6 (IL-6) was produced by irradiation-resistant cells in a biphasic manner, with late IL-6 being absolutely essential for viral control. The underlying mechanism involved IL-6 signaling on virus-specific CD4 T cells that caused up-regulation of the transcription factor Bcl6 and enhanced T follicular helper cell responses at late, but not early, stages of chronic viral infection. This resulted in escalation of germinal center reactions and improved antibody responses. Our results uncover an antiviral strategy that helps to safely resolve a persistent infection in vivo.

1 Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.

* To whom correspondence should be addressed. E-mail: eizuniga{at}

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Y. Xu, C. Weatherall, M. Bailey, S. Alcantara, R. De Rose, J. Estaquier, K. Wilson, K. Suzuki, J. Corbeil, D. A. Cooper, et al. (2013)
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Cutting Edge: STAT1 Is Required for IL-6-Mediated Bcl6 Induction for Early Follicular Helper Cell Differentiation.
Y. S. Choi, D. Eto, J. A. Yang, C. Lao, and S. Crotty (2013)
J. Immunol. 190, 3049-3053
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B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1.
A. Karnowski, S. Chevrier, G. T. Belz, A. Mount, D. Emslie, K. D'Costa, D. M. Tarlinton, A. Kallies, and L. M. Corcoran (2012)
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T. C. Moore, K. L. Bush, L. Cody, D. M. Brown, and T. M. Petro (2012)
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Context-specific roles for paracrine IL-6 in lymphomagenesis.
L. A. Gilbert and M. T. Hemann (2012)
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The origins, function, and regulation of T follicular helper cells.
C. S. Ma, E. K. Deenick, M. Batten, and S. G. Tangye (2012)
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J. M. Clingan, K. Ostrow, K. A. Hosiawa, Z. J. Chen, and M. Matloubian (2012)
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