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). 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.
de Bree
Godelieve J
GJ
Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands. g.j.debree@amc.uva.nl
Daniels
Hans
H
Schilfgaarde
Muriel van
Mv
Jansen
Henk M
HM
Out
Theo A
TA
van Lier
Rene A W
RA
Jonkers
Rene E
RE
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*