title: Respiratory syncytial virus-specific CD8+ memory T cell responses in elderly persons.
abstract: BACKGROUND
  We investigated respiratory syncytial virus (RSV)-specific CD8(+) memory T cell responses in healthy control participants (n=31) and in patients with chronic obstructive pulmonary disease (COPD) (n=9), with respect to frequency, memory phenotype, and proliferative requirements.
  
  
  METHODS
  The properties of RSV-specific CD8(+) T cells were analyzed by use of RSV tetramers. The proliferative requirements of RSV-specific CD8(+) T cells were analyzed by culture of peripheral-blood mononuclear cells with RSV peptide in combination with distinct cytokines.
  
  
  RESULTS
  RSV-specific CD8(+) memory T cells showed a high level of expression of CD27 and interleukin-7R alpha and a low level of expression of CCR7. In the healthy participants, the frequency of RSV tetramer(+) CD8(+) T cells was significantly lower than the frequency of influenza virus A (FLU) tetramer(+) CD8(+) T cells (P=.0001). In contrast to FLU tetramer(+) CD8(+) T cells, we could detect RSV tetramer(+) CD8(+) T cells in the subgroup of elderly healthy participants (age, > or =55 years) and in the patients with COPD only after in vitro expansion. Expanded RSV-specific T cells produced interferon- gamma and granzyme B.
  
  
  CONCLUSIONS
  We provide evidence that a pool of functional RSV-specific CD8(+) memory T cells persists in the peripheral blood of healthy individuals and patients with COPD. Low numbers of RSV-specific memory T cells in the elderly and in patients with COPD may explain the increased susceptibility to RSV infection in these populations.
authors.affiliation: Department of Pulmonology, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands. g.j.debree@amc.uva.nl
authors.forename: Godelieve J
authors.initials: GJ
authors.lastname: de Bree
authors.forename: Jojanneke
authors.initials: J
authors.lastname: Heidema
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.forename: Grada M
authors.initials: GM
authors.lastname: van Bleek
authors.forename: René E
authors.initials: RE
authors.lastname: Jonkers
authors.forename: Henk M
authors.initials: HM
authors.lastname: Jansen
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Theo A
authors.initials: TA
authors.lastname: Out
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D008562:Membrane Glycoproteins; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C515370:CCR7 protein, human; D018106:CD28 Antigens; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D020395:Receptors, Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C415350:interleukin-7 receptor, alpha chain; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1