title: Characterization of CD4+ memory T cell responses directed against common respiratory pathogens in peripheral blood and lung.
abstract: BACKGROUND
  We investigated CD4(+) memory T cell responses to influenza virus (FLU), respiratory syncytial virus (RSV), and nontypeable Haemophilus influenzae (NTHi).
  
  
  METHODS
  The precursor frequencies of antigen-specific CD4(+) cells were determined by in vitro expansion of peripheral blood mononuclear cells from healthy individuals (n=9) and patients with chronic obstructive pulmonary disease (COPD; n=16). The expression of CD27 and CCR7 and the production of interferon (IFN)- gamma and interleukin-2 was measured directly ex vivo. Furthermore, the phenotypic and functional properties of CD4(+) T cells residing in the lung were analyzed and compared with those of circulating CD4(+)memory cells from the same donors (n=8).
  
  
  RESULTS
  FLU-, RSV-, and NTHi-specific CD4(+) memory T cells circulated at low frequencies in the peripheral blood of healthy individuals and patients. RSV- and NTHi-specific CD4(+) T cells had a memory phenotype with moderate to high CD27 and CCR7 expression. In contrast to the low frequencies of circulating FLU-specific CD4(+) T cells, we found an enrichment of differentiated CD4(+) FLU-specific cells and high IFN- gamma expression in CD4(+) memory cells in lung tissue.
  
  
  CONCLUSIONS
  No gross defects were found in circulating CD4(+) memory cells specific for pathogens associated with COPD. However, the large differentiated CD4(+) memory T cell pool residing in the lung may contribute to a large extent to local antiviral immunological protection.
authors.affiliation: Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands. g.j.debree@amc.uva.nl
authors.forename: Godelieve J
authors.initials: GJ
authors.lastname: de Bree
authors.forename: Hans
authors.initials: H
authors.lastname: Daniels
authors.forename: Muriel van
authors.initials: Mv
authors.lastname: Schilfgaarde
authors.forename: Henk M
authors.initials: HM
authors.lastname: Jansen
authors.forename: Theo A
authors.initials: TA
authors.lastname: Out
authors.forename: Rene A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Rene E
authors.initials: RE
authors.lastname: Jonkers
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D006192:Haemophilus Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*