Co-stimulation with TIMs

Bird, Lucy

doi:10.1038/nri1634

Research Highlight
Published: 01 May 2005

Immune regulation

Co-stimulation with TIMs

Lucy Bird

Nature Reviews Immunology volume 5, page 356 (2005)Cite this article

1088 Accesses
Metrics details

Access through your institution

Buy or subscribe

The TIM gene family has eight members in mice and three in humans, all of which are predicted to encode transmembrane proteins that have an IgV domain, a mucin-like domain and a cytoplasmic tail. Umetsu et al. focused their studies on the function of TIM1, whereas Meyers et al. sought to elucidate the role of TIM4 in the immune system.

Using a monoclonal antibody specific for mouse TIM1, Umetsu et al. first showed that TIM1 was expressed by activated T cells and by T cells cultured in T helper 2 (T_H2)-cell-polarizing conditions, and it was absent or present at low levels in resting T cells and T_H1 cells, respectively. By contrast, Meyers et al. showed that TIM4 was not expressed by T cells but was expressed by antigen-presenting cells, with the highest expression levels by mature dendritic cells of the lymphoid lineage. To identify the ligand for TIM4, Meyers et al. generated a TIM4–immunoglobulin fusion protein. The fusion protein specifically bound activated (but not resting) B and T cells, which led the authors to propose that the TIM4 ligand could be TIM1. To confirm this, they showed that the TIM4 fusion protein bound TIM1-expressing cells, and conversely, a TIM1 fusion protein bound TIM4-expressing cells but not untransfected cells or cells expressing other TIM-family members. Moreover, consistent with the TIM1 expression pattern described by Umetsu et al., the TIM4 fusion protein showed a higher level of binding to activated T_H2 cells than to T_H1 cells.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

Purchase on SpringerLink
Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

ORIGINAL RESEARCH PAPERS

Umetsu, S. E. et al. TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nature Immunol. 6, 447–454 (2005).
Article CAS Google Scholar
Meyers, J. H. et al. TIM-4 is the ligand for TIM-1, and the TIM-1–TIM-4 interaction regulates T cell proliferation. Nature Immunol. 6, 455–464 (2005).
Article CAS Google Scholar