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Haartman Institute,
* Department of Virology and
Department of Immunology, University of Helsinki, Finland;
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655;
Medical School, University of Tampere and
¶ Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; and
|| HUSLAB, Helsinki University Hospital, Helsinki, Finland
The induction and maintenance of T cell memory is incompletely understood, especially in humans. We have studied the T cell response and the generation of memory during acute infection by the Puumala virus (PUUV), a hantavirus endemic to Europe. It causes a self-limiting infection with no viral persistence, manifesting as hemorrhagic fever with renal syndrome. HLA tetramer staining of PBMC showed that the CD8+ T cell response peaked at the onset of the clinical disease and decreased within the next 3 wk. Expression of activation markers on the tetramer-positive T cells was also highest during the acute phase, suggesting that the peak population consisted largely of effector cells. Despite the presence of tetramer-positive T cells expressing cytoplasmic IFN-
, PUUV-specific cells producing IFN- in vitro were rare during the acute phase. Their frequency, as well as the expression of IL-7R
mRNA and surface protein, increased during a follow-up period of 6 wk and probably reflected the induction of memory T cells. Simultaneously with the PUUV-specific response, we also noted in seven of nine patients an increase in EBV-specific T cells and the transient presence of EBV DNA in three patients, indicative of viral reactivation. Our results show that in a natural human infection CD8+ memory T cells are rare during the peak response, gradually emerging during the first weeks of convalescence. They also suggest that the boosting of unrelated memory T cells may be a common occurrence in human viral infections, which may have significant implications for the homeostasis of the memory T cell compartment.
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 grants from the Academy of Finland, the Sigrid Jusélius Foundation, the Finnish Technology Advancement Fund, the Finnish Cancer Research Foundation, the Helsinki University Central Hospital Research and Education Fund, and the Medical Research Fund of Tampere University Hospital, European Commission Contracts QLK2-CT-1999-01119 and GLK2-CT-2002-01358, and National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant U19 AI057319.
2 T.T. and E.K. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. T. Petteri Arstila, Haartman Institute, Department of Immunology, PB21, University of Helsinki, Finland. E-mail address: petteri.arstila{at}helsinki.fi
4 Abbreviations used in this paper: PUUV, Puumala virus; N, nucleocapsid protein; NE, nephropathia epidemica.
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