This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ruckwardt, T. J. Articles by Graham, B. S. Search for Related Content PubMed PubMed Citation Articles by Ruckwardt, T. J. Articles by Graham, B. S.

 Previous Article  |  Next Article 

Journal of Virology, April 2009, p. 3019-3028, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.00036-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Regulatory T Cells Promote Early Influx of CD8⁺ T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities ^,

Tracy J. Ruckwardt,¹ Kathryn L. Bonaparte,¹ Martha C. Nason,² and Barney S. Graham^1*

Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infections Diseases, National Institutes of Health, Bethesda, Maryland,¹ Biostatistics Research Branch, National Institute of Allergy and Infections Diseases, National Institutes of Health, Bethesda, Maryland²

Received 5 December 2008/ Accepted 9 January 2009

In addition to regulating autoimmunity and antitumor immunity, CD4⁺ CD25⁺ FoxP3⁺ natural regulatory T (Treg) cells are global regulators of adaptive immune responses. Depletion of these cells with the anti-CD25 antibody PC61 prior to primary respiratory syncytial virus (RSV) infection was partial but had several effects on the RSV-specific CD8⁺ response in a hybrid mouse model. Mediastinal lymph node and spleen epitope-specific CD8⁺ T-cell responses were enhanced in Treg-cell-depleted mice at all time points following infection, but responses of Treg-cell-depleted lung show a strikingly different pattern than lymphoid organ responses, with an initial delay in the CD8⁺ T-cell response. The delay in the CD8⁺ T-cell response correlated with a delay both in the early phase of viral clearance and in illness in Treg-cell-depleted mice compared to isotype-treated controls. The lungs of Treg-cell-depleted mice were shown to have increased lung chemokine and cytokine levels 7 days postinfection despite lower CD8⁺ T-cell responses. Following the early delay in the lung response, CD8⁺ T-cell responses at later infection time points were enhanced and increased the severity of illness in depleted mice. Finally, decreasing regulatory T-cell control of the CD8⁺ T-cell response had a greater effect on response of the dominant K^d-restricted M2 epitope consisting of amino acids 82 to 90 (K^dM2_82-90) than on the subdominant D^bM_187-195 epitope response, indicating that regulatory T cells modulate immunodominance disparities in epitope-specific CD8⁺ T-cell responses following primary RSV infection.

---

* Corresponding author. Mailing address: Vaccine Research Center, National Institute of Allergy and Infections Diseases, National Institutes of Health, 40 Convent Dr., Bethesda, MD 20892. Phone: (301) 594-8468. Fax: (301) 480-2771. E-mail: bgraham{at}nih.gov

Published ahead of print on 19 January 2009.

Supplemental material for this article may be found at http://jvi.asm.org/.

---

Journal of Virology, April 2009, p. 3019-3028, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.00036-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.