Accumulation of gamma/delta T cells in the lungs and their roles in neutrophil-mediated host defense against pneumococcal infection.
The present study was designed to elucidate the role of Vgamma4(+) gammadelta T cells, a major subset of pulmonary gammadelta T cells, in host defense against infection with Streptococcus pneumoniae. The proportion and number of whole gammadelta T cells, identified as CD3(+) and TCR-delta(+) cells, and Vgamma4(+) gammadelta T cells, identified as CD3(+) and TCR-Vgamma4(+) cells, increased in the lungs at 3, 6 and 12h post-infection. Survival of infected mice and lung bacterial clearance were severely impaired in TCR-Vgamma4(-/-) mice compared with control wild-type (WT) mice. The impaired host protection in TCR-Vgamma4(-/-) mice correlated well with attenuated recruitment of neutrophils in lungs. MIP-2 and TNF-alpha synthesis in the infected tissues was significantly reduced in TCR-Vgamma4(-/-) mice compared with WT mice. Similar results were noted in the synthesis of TNF-alpha, but not clearly of MIP-2, by lung leukocytes stimulated with live bacteria. Our results demonstrate that Vgamma4(+) gammadelta T cells play an important role in the neutrophil-mediated host defense against S. pneumoniae infection by promoting the synthesis of TNF-alpha and possibly of MIP-2 in the lungs.
Nakasone
Chikara
C
Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Yamamoto
Natsuo
N
Nakamatsu
Masashi
M
Kinjo
Takeshi
T
Miyagi
Kazuya
K
Uezu
Kaori
K
Nakamura
Kiwamu
K
Higa
Futoshi
F
Ishikawa
Hiromichi
H
O'brien
Rebecca L
RL
Ikuta
Koichi
K
Kaku
Mitsuo
M
Fujita
Jiro
J
Kawakami
Kazuyoshi
K
D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014774:Virulence
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha