title: 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.
abstract: 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.
authors.affiliation: Haartman Institute, University of Helsinki, Finland.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tuuminen
authors.forename: Eliisa
authors.initials: E
authors.lastname: Kekäläinen
authors.forename: Satu
authors.initials: S
authors.lastname: Mäkelä
authors.forename: Ilpo
authors.initials: I
authors.lastname: Ala-Houhala
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: Klaus
authors.initials: K
authors.lastname: Hedman
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D018778:Hantavirus Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D053720:Interleukin-15 Receptor alpha Subunit / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D029262:Puumala virus / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D014775:Virus Activation / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D053720:Interleukin-15 Receptor alpha Subunit; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain