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Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells

Science, 30 May 2008
Vol. 320, Issue 5880, p. 1220-1224
DOI: 10.1126/science.1155209

Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells

  1. Jennifer M. Lund,
  2. Lianne Hsing,
  3. Thuy T. Pham,
  4. Alexander Y. Rudensky*
  1. Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
  1. * To whom correspondence should be addressed. E-mail: aruden{at}u.washington.edu

Abstract

Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue.

  • Received for publication 14 January 2008.
  • Accepted for publication 11 April 2008.

Citation:

J. M. Lund, L. Hsing, T. T. Pham, and A. Y. Rudensky, Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells. Science 320, 1220-1224 (2008).

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Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response
O. Feinerman, G. Jentsch, K. E. Tkach, J. W. Coward, M. M. Hathorn, M. W. Sneddon, T. Emonet, K. A. Smith, and G. Altan-Bonnet
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J. Immunol. 193, 871-878 (15 July 2014)

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JEM 211, 961-974 (5 May 2014)

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X. Chen, and J. J. Oppenheim
J. Leukoc. Biol. 95, 723-731 (1 May 2014)

Interindividual variation in human T regulatory cells
A. Ferraro, A. M. D'Alise, T. Raj, N. Asinovski, R. Phillips, A. Ergun, J. M. Replogle, A. Bernier, L. Laffel, B. E. Stranger et al.
Proc. Natl. Acad. Sci. USA 111, E1111-E1120 (25 March 2014)

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E. H. Kim, D. J. Gasper, S. H. Lee, E. H. Plisch, J. Svaren, and M. Suresh
J. Immunol. 192, 985-995 (1 February 2014)

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J. Immunol. 192, 683-690 (15 January 2014)

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Proc. Natl. Acad. Sci. USA 110, 21089-21094 (24 December 2013)

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A. R. M. Kraft, M. F. Wlodarczyk, L. L. Kenney, and L. K. Selin
J. Virol. 87, 12636-12647 (1 December 2013)

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S. Angiari, B. Rossi, L. Piccio, B. H. Zinselmeyer, S. Budui, E. Zenaro, V. Della Bianca, S. D. Bach, E. Scarpini, M. Bolomini-Vittori et al.
J. Immunol. 191, 5489-5500 (1 December 2013)

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L. R. Durant, S. Makris, C. M. Voorburg, J. Loebbermann, C. Johansson, and P. J. M. Openshaw
J. Virol. 87, 10946-10954 (15 October 2013)

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K. Venken, T. Decruy, S. Aspeslagh, S. Van Calenbergh, B. N. Lambrecht, and D. Elewaut
J. Immunol. 191, 2174-2183 (1 September 2013)

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T. A. Cheema, H. Wakimoto, P. E. Fecci, J. Ning, T. Kuroda, D. S. Jeyaretna, R. L. Martuza, and S. D. Rabkin
Proc. Natl. Acad. Sci. USA 110, 12006-12011 (16 July 2013)

Viral Antigen Induces Differentiation of Foxp3+ Natural Regulatory T Cells in Influenza Virus-Infected Mice
F. Bedoya, G.-S. Cheng, A. Leibow, N. Zakhary, K. Weissler, V. Garcia, M. Aitken, E. Kropf, D. S. Garlick, E. J. Wherry et al.
J. Immunol. 190, 6115-6125 (15 June 2013)

Rift Valley Fever Virus Clearance and Protection from Neurologic Disease Are Dependent on CD4+ T Cell and Virus-Specific Antibody Responses
K. A. Dodd, A. K. McElroy, M. E. B. Jones, S. T. Nichol, and C. F. Spiropoulou
J. Virol. 87, 6161-6171 (1 June 2013)

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E. Dominguez-Huttinger, M. Ono, M. Barahona, and R. J. Tanaka
Interface Focus 3, 20120090-20120090 (21 February 2013)

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R. Nasser, M. Pelegrin, M. Plays, L. Gros, and M. Piechaczyk
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T. Veiga-Parga, A. Suryawanshi, S. Mulik, F. Gimenez, S. Sharma, T. Sparwasser, and B. T. Rouse
J. Immunol. 189, 5924-5933 (15 December 2012)

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L. Pace, A. Tempez, C. Arnold-Schrauf, F. Lemaitre, P. Bousso, L. Fetler, T. Sparwasser, and S. Amigorena
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C. Y. Chen, D. Huang, S. Yao, L. Halliday, G. Zeng, R. C. Wang, and Z. W. Chen
J. Immunol. 188, 4278-4288 (1 May 2012)

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L. Cervantes-Barragan, S. Firner, I. Bechmann, A. Waisman, K. Lahl, T. Sparwasser, V. Thiel, and B. Ludewig
J. Immunol. 188, 3678-3685 (15 April 2012)

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U. Hofmann, N. Beyersdorf, J. Weirather, A. Podolskaya, J. Bauersachs, G. Ertl, T. Kerkau, and S. Frantz
Circulation 125, 1652-1663 (3 April 2012)

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R. J. Betts, N. Prabhu, A. W. S. Ho, F. C. Lew, P. E. Hutchinson, O. Rotzschke, P. A. Macary, and D. M. Kemeny
J. Virol. 86, 2817-2825 (1 March 2012)

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A. Benson, S. Murray, P. Divakar, N. Burnaevskiy, R. Pifer, J. Forman, and F. Yarovinsky
J. Immunol. 188, 800-810 (15 January 2012)

Tregs and infections: on the potential value of modifying their function
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J. Leukoc. Biol. 90, 1079-1087 (1 December 2011)

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B. Baban, P. R. Chandler, B. A. Johnson, L. Huang, M. Li, M. L. Sharpe, L. M. Francisco, A. H. Sharpe, B. R. Blazar, D. H. Munn et al.
J. Immunol. 187, 2329-2335 (1 September 2011)

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T.-L. M. Nguyen, N. L. Sullivan, M. Ebel, R. M. Teague, and R. J. DiPaolo
J. Immunol. 187, 1745-1753 (15 August 2011)

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A. L. Mellor, and D. H. Munn
J. Immunol. 186, 4535-4540 (15 April 2011)

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K. D. Nguyen, C. Macaubas, K. C. Nadeau, P. Truong, T. Yoon, T. Lee, J. L. Park, and E. D. Mellins
Blood 117, 3793-3798 (7 April 2011)

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M. Mohamadzadeh, E. A. Pfeiler, J. B. Brown, M. Zadeh, M. Gramarossa, E. Managlia, P. Bere, B. Sarraj, M. W. Khan, K. C. Pakanati et al.
Proc. Natl. Acad. Sci. USA 108, 4623-4630 (15 March 2011)

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G. A. Punkosdy, M. Blain, D. D. Glass, M. M. Lozano, L. O'Mara, J. P. Dudley, R. Ahmed, and E. M. Shevach
Proc. Natl. Acad. Sci. USA 108, 3677-3682 (1 March 2011)

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U. Schenk, M. Frascoli, M. Proietti, R. Geffers, E. Traggiai, J. Buer, C. Ricordi, A. M. Westendorf, and F. Grassi
Sci Signal 4, ra12-ra12 (1 March 2011)

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C. D. Conrady, W. P. Halford, and D. J. J. Carr
J. Virol. 85, 1625-1633 (15 February 2011)

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J. Schulze zur Wiesch, A. Thomssen, P. Hartjen, I. Toth, C. Lehmann, D. Meyer-Olson, K. Colberg, S. Frerk, D. Babikir, S. Schmiedel et al.
J. Virol. 85, 1287-1297 (1 February 2011)

Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue
N. Iijima, L. M. Mattei, and A. Iwasaki
Proc. Natl. Acad. Sci. USA 108, 284-289 (4 January 2011)

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I. Antunes, and G. Kassiotis
J. Virol. 84, 12564-12575 (15 December 2010)

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Y. Wang, A. Souabni, R. A. Flavell, and Y. Y. Wan
J. Immunol. 185, 5983-5992 (15 November 2010)

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L. E. Yauch, T. R. Prestwood, M. M. May, M. M. Morar, R. M. Zellweger, B. Peters, A. Sette, and S. Shresta
J. Immunol. 185, 5405-5416 (1 November 2010)

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T. Chinen, P. Y. Volchkov, A. V. Chervonsky, and A. Y. Rudensky
JEM 207, 2323-2330 (25 October 2010)

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J. Liu, T. J. Ruckwardt, M. Chen, J. D. Nicewonger, T. R. Johnson, and B. S. Graham
J. Virol. 84, 10501-10509 (15 October 2010)

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D. C. P. Lee, J. A. E. Harker, J. S. Tregoning, S. F. Atabani, C. Johansson, J. Schwarze, and P. J. M. Openshaw
J. Virol. 84, 8790-8798 (1 September 2010)

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R. B. Fulton, D. K. Meyerholz, and S. M. Varga
J. Immunol. 185, 2382-2392 (15 August 2010)

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T. G. Jones, F. D. Finkelman, K. F. Austen, and M. F. Gurish
J. Immunol. 185, 1804-1811 (1 August 2010)

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S. A. Joosten, and T. H. M. Ottenhoff
J. Immunol. 185, 1351-1351 (1 August 2010)

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E.-J. Freyschmidt, C. B. Mathias, N. Diaz, D. H. MacArthur, A. Laouar, N. Manjunath, M. D. Hofer, M.-A. Wurbel, J. J. Campbell, T. A. Chatila et al.
J. Immunol. 185, 1295-1302 (15 July 2010)

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A. Khanolkar, R. B. Fulton, L. L. Epping, N.-L. Pham, D. Tifrea, S. M. Varga, and J. T. Harty
J. Immunol. 185, 1132-1141 (15 July 2010)

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S. Shafiani, G. Tucker-Heard, A. Kariyone, K. Takatsu, and K. B. Urdahl
JEM 207, 1409-1420 (5 July 2010)

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C. J. Winstead, C. S. Reilly, J. J. Moon, M. K. Jenkins, S. E. Hamilton, S. C. Jameson, S. S. Way, and A. Khoruts
J. Immunol. 184, 4749-4760 (1 May 2010)

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K. Trandem, D. Anghelina, J. Zhao, and S. Perlman
J. Immunol. 184, 4391-4400 (15 April 2010)

Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice
Y. Ozeki, I. Sugawara, T. Udagawa, T. Aoki, M. Osada-Oka, Y. Tateishi, H. Hisaeda, Y. Nishiuchi, N. Harada, K. Kobayashi et al.
Int Immunol 22, 179-189 (1 March 2010)

Mechanisms of control of acute Friend virus infection by CD4+ T helper cells and their functional impairment by regulatory T cells
S. R. Nair, G. Zelinskyy, S. Schimmer, N. Gerlach, G. Kassiotis, and U. Dittmer
J. Gen. Virol. 91, 440-451 (1 February 2010)

Human Immunodeficiency Virus Type 1 Mediates Global Disruption of Innate Antiviral Signaling and Immune Defenses within Infected Cells
B. P. Doehle, F. Hladik, J. P. McNevin, M. J. McElrath, and M. Gale
J. Virol. 83, 10395-10405 (15 October 2009)

The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response
G. Zelinskyy, K. K. Dietze, Y. P. Husecken, S. Schimmer, S. Nair, T. Werner, K. Gibbert, O. Kershaw, A. D. Gruber, T. Sparwasser et al.
Blood 114, 3199-3207 (8 October 2009)

How Diverse--CD4 Effector T Cells and their Functions
Y. Y. Wan, and R. A. Flavell
J Mol Cell Biol 1, 20-36 (1 October 2009)

Superantigen-Activated Regulatory T Cells Inhibit the Migration of Innate Immune Cells and the Differentiation of Naive T Cells
Y. Tanriver, A. Martin-Fontecha, K. Ratnasothy, G. Lombardi, and R. Lechler
J. Immunol. 183, 2946-2956 (1 September 2009)

CD4+ CD25+ Foxp3- T-Regulatory Cells Produce both Gamma Interferon and Interleukin-10 during Acute Severe Murine Spotted Fever Rickettsiosis
R. Fang, N. Ismail, T. Shelite, and D. H. Walker
Infect. Immun. 77, 3838-3849 (1 September 2009)

The Initial Phase of an Immune Response Functions to Activate Regulatory T Cells
W. E. O'Gorman, H. Dooms, S. H. Thorne, W. F. Kuswanto, E. F. Simonds, P. O. Krutzik, G. P. Nolan, and A. K. Abbas
J. Immunol. 183, 332-339 (1 July 2009)

GITR Triggering Induces Expansion of Both Effector and Regulatory CD4+ T Cells In Vivo
R. W. van Olffen, N. Koning, K. P. J. M. van Gisbergen, F. M. Wensveen, R. M. Hoek, L. Boon, J. Hamann, R. A. W. van Lier, and M. A. Nolte
J. Immunol. 182, 7490-7500 (15 June 2009)

Anti-CD25 Antibody-Mediated Depletion of Effector T Cell Populations Enhances Susceptibility of Mice to Acute but Not Chronic Toxoplasma gondii Infection
K. N. Couper, P. A. Lanthier, G. Perona-Wright, L. W. Kummer, W. Chen, S. T. Smiley, M. Mohrs, and L. L. Johnson
J. Immunol. 182, 3985-3994 (1 April 2009)

Regulatory T Cells Promote Early Influx of CD8+ T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities
T. J. Ruckwardt, K. L. Bonaparte, M. C. Nason, and B. S. Graham
J. Virol. 83, 3019-3028 (1 April 2009)

Intratumoral Immune Cell Infiltrates, FoxP3, and Indoleamine 2,3-Dioxygenase in Patients with Melanoma Undergoing CTLA4 Blockade
A. Ribas, B. Comin-Anduix, J. S. Economou, T. R. Donahue, P. de la Rocha, L. F. Morris, J. Jalil, V. B. Dissette, I. P. Shintaku, J. A. Glaspy et al.
Clin. Cancer Res. 15, 390-399 (1 January 2009)

Lymphocytes in action: Symposium on Lymphocyte Activation and Signalling
W.-K. Suh, and J. Chaudhuri
EMBO Rep. 9, 841-846 (1 September 2008)

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G. Kassiotis, and A. O'Garra
Science 320, 1168-1169 (30 May 2008)

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