Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti-Tim-3 antibody in vivo.
T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) is a surface molecule that is preferentially expressed on activated Th1 cells in comparison to Th2 cells. Blockade of Tim-3 has been shown to enhance Th1-driven pathology in vivo, suggesting that blockade of Tim-3 may improve the development of Th2-associated responses such as allergy. To examine the effects of Tim-3 blockade on the Th2 response in vivo, we administered anti-Tim-3 antibody during pulmonary inflammation induced by transfer of ovalbumin (OVA)-reactive Th2 cells, and subsequent aerosol challenge with OVA. In this model, anti-Tim-3 antibody treatment before each airway challenge significantly reduced airway hyperreactivity, with a concomitant decrease in eosinophils and Th2 cells in the lung. We examined Th1 and Th2 cytokine levels in the lung after allergen challenge and found that pulmonary expression of the Th2 cytokine IL-5 was significantly reduced, whereas IFN-gamma levels were significantly increased by anti-Tim-3 antibody treatment. Thus, blocking Tim-3 function has a beneficial effect during pulmonary inflammation by skewing the Th2 response toward that of a Th1 type, suggesting an important role for Tim-3 in the regulation of allergic disease.
Kearley
Jennifer
J
Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London SW7 2AZ, England, UK.
McMillan
Sarah J
SJ
Lloyd
Clare M
CM
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000906:Antibodies; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D015848:Interleukin-5; D008565:Membrane Proteins; D007371:Interferon-gamma; D010047:Ovalbumin