TIM-4 is the ligand for TIM-1, and the TIM-1–TIM-4 interaction regulates T cell proliferation

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Abstract
The newly identified TIM family of proteins is associated with regulation of T helper type 1 (TH1) and TH2 immune responses. TIM-1 is genetically linked to asthma and is a receptor for hepatitis A virus, but the endogenous ligand of TIM-1 is not known. Here we show that TIM-4, which is expressed by antigen-presenting cells, is the ligand for TIM-1. In vivo administration of either soluble TIM-1–immunoglobulin (TIM-1–Ig) fusion protein or TIM-4–Ig fusion protein resulted in hyperproliferation of T cells, and TIM-4–Ig costimulated T cell proliferation mediated by CD3 and CD28 in vitro. These data suggest that the TIM-1–TIM-4 interaction is involved in regulating T cell proliferation.