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Irene D Sizing, Véronique Bailly, Patricia McCoon, Wenjie Chang, Sambasiva Rao, Lourdes Pablo, Rachel Rennard, Meghan Walsh, Zhifang Li, Mohammad Zafari, Max Dobles, Leticia Tarilonte, Steven Miklasz, Gerard Majeau, Kevin Godbout, Martin L Scott, Paul D Rennert, Epitope-Dependent Effect of Anti-Murine TIM-1 Monoclonal Antibodies on T Cell Activity and Lung Immune Responses, The Journal of Immunology, Volume 178, Issue 4, February 2007, Pages 2249–2261, https://doi.org/10.4049/jimmunol.178.4.2249
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Abstract
The TAPR locus containing the TIM gene family is implicated in the development of atopic inflammation in mouse, and TIM-1 allelic variation has been associated with the incidence of atopy in human patient populations. In this study, we show that manipulation of the TIM-1 pathway influences airway inflammation and pathology. Anti-TIM-1 mAbs recognizing distinct epitopes differentially modulated OVA-induced lung inflammation in the mouse. The epitopes recognized by these Abs were mapped, revealing that mAbs to both the IgV and stalk domains of TIM-1 have therapeutic activity. Unexpectedly, mAbs recognizing unique epitopes spanning exon 4 of the mucin/stalk domains exacerbated immune responses. Using Ag recall response studies, we demonstrate that the TIM-1 pathway acts primarily by modulating the production of TH2 cytokines. Furthermore, ex vivo cellular experiments indicate that TIM-1 activity controls CD4+ T cell activity. These studies validate the genetic hypothesis that the TIM-1 locus is linked to the development of atopic disease and suggest novel therapeutic strategies for targeting asthma and other atopic disorders.