Characterization of CD4+ memory T cell responses directed against common respiratory pathogens in peripheral blood and lung

J Infect Dis. 2007 Jun 1;195(11):1718-25. doi: 10.1086/517612. Epub 2007 Apr 16.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • Haemophilus Infections / complications
  • Haemophilus Infections / immunology
  • Haemophilus Infections / microbiology
  • Haemophilus influenzae / immunology*
  • Humans
  • Immunologic Memory / immunology*
  • Influenza, Human / complications
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Leukocytes, Mononuclear / immunology*
  • Lung / immunology*
  • Lymphocyte Activation
  • Middle Aged
  • Orthomyxoviridae / immunology*
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / immunology*