Modulating the function of T cell immunoglobulin mucin cell surface proteins for therapeutic immunoregulation

Brigham & Womens Hospital, Beth Israel Hospital: WO2005033144 and WO2005090573

T cell immunoglobulin-mucin (TIM) molecules are transmembrane cell surface glycoproteins possessing an immunoglobulin domain and a mucin-like domain in their extracellular region. Recently, several of these molecules have been shown to be differentially expressed by the T helper (T_H)-1 and T_H2 lymphocyte subsets, which are known to differ in their cytokine production and effector functions and to play crucial roles in coordinating immune responses and controlling or promoting the development of autoimmune and allergic diseases. Such TIM proteins, including TIM-1, -2, -3 and -4 in mice, have therefore been regarded as potential regulators of T_H1 and T_H2 activities and immune responses. The two patent applications reviewed show that TIM-1 and TIM-2 are both associated with T_H2 cells, whereas TIM-3 is associated with T_H1 cells, and that TIM-4 and galectin-9 are ligands for TIM-1 and TIM-3, respectively. Furthermore, various reagents targeting these TIM proteins are demonstrated to affect immune functions in experimental murine models. Thus, TIM-1 or -2 modulation selectively altered T_H2-mediated responses, whereas TIM-3 modulation influenced T_H1-mediated responses. Hence, it is claimed that the manipulation of TIM protein functions may provide novel methods for therapeutic immunoregulation in the treatment of immune-based diseases. However, further studies are needed to examine the validity of this claim in human disease situations.