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

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) 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.