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The Journal of Immunology, 2007, 179, 8410 -8417
Copyright © 2007 by The American Association of Immunologists, Inc.

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CD8+ T Cell Responses in Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells of Infants with Severe Primary Respiratory Syncytial Virus Infections1

Jojanneke Heidema*, Michaël V. Lukens*, Wendy W. C. van Maren*, Mariska E. A. van Dijk*, Henny G. Otten{dagger}, Adrianus J. van Vught*, Desiree B. M. van der Werff*, Sjef J. P. van Gestel*, Malcolm G. Semple{ddagger}, Rosalind L. Smyth{ddagger}, Jan L. L. Kimpen* and Grada M. van Bleek2,*

* Division of Pediatrics, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands; {dagger} Department of Immunology, University Medical Center, Utrecht, The Netherlands; and {ddagger} Division of Child Health, University of Liverpool, Institute of Child Health, Alder Hey Children’s Hospital, Liverpool, United Kingdom

A protective role for CD8+ T cells during viral infections is generally accepted, but little is known about how CD8+ T cell responses develop during primary infections in infants, their efficacy, and how memory is established after viral clearance. We studied CD8+ T cell responses in bronchoalveolar lavage (BAL) samples and blood of infants with a severe primary respiratory syncytial virus (RSV) infection. RSV-specific CD8+ T cells with an activated effector cell phenotype: CD27+CD28+CD45RO+CCR7CD38+HLA-DR+Granzyme B+CD127 could be identified in BAL and blood. A high proportion of these CD8+ T cells proliferated and functionally responded upon in vitro stimulation with RSV Ag. Thus, despite the very young age of the patients, a robust systemic virus-specific CD8+ T cell response was elicited against a localized respiratory infection. RSV-specific T cell numbers as well as the total number of activated effector type CD8+ T cells peaked in blood around day 9–12 after the onset of primary symptoms, i.e., at the time of recovery. The lack of a correlation between RSV-specific T cell numbers and parameters of disease severity make a prominent role in immune pathology unlikely, in contrast the T cells might be involved in the recovery process.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was performed without any external funding.

2 Address correspondence and reprint requests to Dr. Grada van Bleek, Department of Pediatric Immunology, The Wilhelmina Children’s Hospital, KE04.133.1, University Medical Center Utrecht, Lundlaan 6, Utrecht, The Netherlands. E-mail address: g.vanbleek{at}umcutrecht.nl

3 Abbreviations used in this paper: RSV, respiratory syncytial virus; BAL, bronchoalveolar lavage; NB-BAL, non-bronchoscopic bronchoalveolar lavage; GzmB, Granzyme B; 7AAD, 7-aminoactinomycin D.




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