The role of the T-cell costimulatory molecule Tim-1 in the immune response.

Upon encountering antigen, CD4+ T-cells become activated and can differentiate into subsets with distinct functional characteristics. One of these subsets is the Th2 cell, which generates large amounts of interleukin (IL)-4, -5, -10 and -13 in response to a subsequent encounter with antigen. In the context of a protective immune response, Th2 cells promote immune cell activation, antibody production, and inflammatory responses that help clear infections. However, aberrant responses by Th2 cells can lead to debilitating allergic diseases such as asthma. Thus, a reasonable approach toward gaining novel insights into immunity and allergic disease is to define the mechanisms that control Th2 cell differentiation and mature Th2 cell function. Recent work suggests that a protein called Tim-1 (T-cell immunoglobulin and mucin protein-1) is expressed on CD4+ T-cells and plays a central role in regulating Th2 responses. Genetic analysis has linked polymorphisms in the human TIM1 gene to susceptibility to allergic disease, while studies involving mice have shown that ligation of Tim-1 promotes CD4+ T-cell activation. The signal transduction pathways downstream of Tim-1 are a relatively unexplored area. Continued study will undoubtedly reveal novel insights regarding the relationships between Tim-1, Th2 responses, and allergic disease.