Human CD8+ T cell memory generation in Puumala hantavirus infection occurs after the acute phase and is associated with boosting of EBV-specific CD8+ memory T cells
Department of Medicine, Division of Infectious Diseases and Immunology; Center for Infectious Disease and Vaccine Research
Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease
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-gamma, PUUV-specific cells producing IFN-gamma in vitro were rare during the acute phase. Their frequency, as well as the expression of IL-7R alpha 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.
DOI of Published Version
J Immunol. 2007 Aug 1;179(3):1988-95. DOI: 10.4049/jimmunol.179.3.1988
Journal of immunology (Baltimore, Md. : 1950)
Tuuminen, Tamara; Kekalainen, Eliisa; Makela, Satu; Ala-Houhala, Ilpo; Ennis, Francis A.; Hedman, Klaus; Mustonen, Jukka; Vaheri, Antti; and Arstila, T Petteri., "Human CD8+ T cell memory generation in Puumala hantavirus infection occurs after the acute phase and is associated with boosting of EBV-specific CD8+ memory T cells" (2007). Infectious Diseases and Immunology Publications and Presentations. 252.