The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury.
Acute lung injury was produced in C57BL/6 mice by the intratracheal (i.t.) administration of bleomycin (BLM). Following injection of 0.1 U BLM, CD3+ lymphocytes and the production of the T-helper-1 (Th1) lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were increased in lung and lymph nodes. The production of the Th2 cytokine IL-4 by lung lymphocytes was decreased. Intraperitoneal (i.p.) injection of a rat antimurine CD3 (YCD3) monoclonal antibody (mAb) blocked the accumulation of pulmonary CD3+ cells for up to 14 d and effectively suppressed IL-2 and IL-4 but not IFN-gamma production by lung lymphocytes throughout the protocol. Secretion of all of the above lymphokines by lymph node cells was inhibited by YCD3 treatment. Administration of YCD3 diminished pulmonary fibrosis and increased survival (p < 0.01) following BLM administration compared with mice treated with an isotype-matched control mAb. Initiating treatment with YCD3 at Days 5-7 following BLM also decreased pulmonary fibrosis and significantly reduced mortality (p < 0.02). We conclude that BLM yields a potentially lethal fibroinflammatory response in the lung that is markedly diminished by antagonizing the functional activities of CD3+ cells in vivo.
Sharma
S K
SK
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
MacLean
J A
JA
Pinto
C
C
Kradin
R L
RL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D008222:Lymphokines; D001761:Bleomycin; D015847:Interleukin-4; D007371:Interferon-gamma