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Dynamics of Human Respiratory Virus-Specific CD8⁺ T Cell Responses in Blood and Airways during Episodes of Common Cold¹

Jojanneke Heidema^*, John W. A. Rossen^2,, Michaël V. Lukens^2,*, Marianne S. Ketel^*, Eva Scheltens^*, Mariette E. G. Kranendonk^*, Wendy W. C. van Maren^*, Anton M. van Loon, Henny G. Otten, Jan L. L. Kimpen^* and Grada M. van Bleek^3,*

^* Division of Paediatrics, Wilhelmina Children’s Hospital, Department of Virology, and Department of Immunology, University Medical Center, Utrecht, the Netherlands

We determined the dynamics of CD8⁺ T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8⁺ T cells to resting memory/naive CD8⁺ T cells in peripheral blood increased significantly. Furthermore, the number of effector/memory T cells specific for respiratory viruses declined in blood and increased in the airways, suggesting that these T cells redistributed from blood to airways. T cells specific for the infecting virus were present in the airways for longer periods at increased levels than nonspecifically recruited bystander T cells. After clearance of the infection, the ratio of resting memory and naive CD8⁺ T cells normalized in peripheral blood and also memory T cell numbers specific for unrelated viruses that declined during the infection due to bystander recruitment were restored. Taken together, these results showed a significant systemic T cell response during relatively mild secondary infections and extensive dynamics of virus-specific and nonspecific Ag-experienced T cells.

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 supported by the Wilhelmina Research Fund.

² J.W.A.R. and M.V.L. equally contributed to this work.

³ 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, 3584 CX Utrecht, The Netherlands. E-mail address: g.vanbleek{at}umcutrecht.nl

⁴ Abbreviations used in this paper: RSV, respiratory syncytial virus; GzmB, granzyme B; moi, multiplicity of infection; RT, reverse transcriptase.