Chemokine expression in Th1 cell-induced lung injury: prominence of IFN-gamma-inducible chemokines.
Proinflammatory responses generated by T helper type 1 (Th1) cells may contribute significantly to immune-mediated lung injury. We describe a murine model of Th1 cell-induced lung injury in which adoptive transfer of alloreactive Th1 cells produces pulmonary inflammation characterized by mononuclear cell vasculitis, alveolitis, and interstitial pneumonitis. To investigate the link between activation of Th1 cells in the lung and inflammatory cell recruitment, we characterized cytokine and chemokine mRNA expression in Th1 cells activated in vitro and in lung tissue after adoptive transfer of Th1 cells. Activated Th1 cells per se express mRNA for interferon (IFN)-gamma and several members of the tumor necrosis factor family as well as the C-C chemokine receptor-5 ligands regulated on activation normal T cells expressed and secreted and macrophage inflammatory protein-1alpha and -1beta. Additional chemokine genes were induced in the lung after Th1 cell administration, most notably IFN-gamma-inducible protein (IP-10) and monokine induced by IFN-gamma (MIG). Remarkable increases in IP-10- and MIG-immunoreactive proteins were present in inflammatory foci lung and identified in macrophages, endothelium, bronchial epithelium, and alveolar structures. The findings suggest that IFN-gamma-inducible chemokines are an important mechanism for amplifying inflammation initiated by Th1 cells in the lung.
Dixon
A E
AE
Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA.
Mandac
J B
JB
Madtes
D K
DK
Martin
P J
PJ
Clark
J G
JG
D000818:Animals; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018417:Th1 Cells / Q000276:immunology*
C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma