T cell pathways involving CTLA4 contribute to a model of acute lung injury.
Acute lung injury (ALI) is a frequent pulmonary complication in critically ill patients. We characterized a murine model of LPS-induced ALI, focusing on Th cells. Following LPS administration, bronchoalveolar lavage lymphocytes, neutrophils, IL-6, TNF-alpha, and albumin were increased. Analysis of LPS-induced T cells revealed increased Th cell-associated cytokines (IL-17A, -17F, and -22), as well as increased expression of CD69 (a cell activation marker), Foxp3, and CTLA4 in CD4(+) T cells. Administration of anti-CTLA4 Ab decreased LPS-induced bronchoalveolar lavage albumin and IL-17A, while increasing CD4(+)Foxp3(+) cell number and Foxp3 expression in CD4(+)Foxp3(+) cells. These data suggest that pulmonary LPS administration promotes CD4(+) T cells and that T cell pathways involving CTLA4 contribute to ALI.
Nakajima
Takeshi
T
Division of Pulmonary and Critical Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Suarez
Carlos Jose
CJ
Lin
Ko-Wei
KW
Jen
Kai Yu
KY
Schnitzer
Jan E
JE
Makani
Samir S
SS
Parker
Nathan
N
Perkins
David L
DL
Finn
Patricia W
PW
D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D060908:CTLA-4 Antigen; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000502:physiology / Q000633:toxicity; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018836:Inflammation Mediators; D008070:Lipopolysaccharides
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