Comment on “CRTAM Confers Late-Stage Activation of CD8+ T Cells to Regulate Retention within Lymph Node”

Abstract

Takeuchi et al.’s elegant study in the October 1, 2009 issue of The Journal of Immunology (1) demonstrates that CD8 T cells, which express class I-restricted T cell-associated molecule (CRTAM) during activation, bind to CADM1 (Necl-2) expressing CD11c+ dendritic cells in lymph nodes. Notably, this interaction is important for CD8+ T cell retention within the lymph node and contributes to development of an autoimmune disorder. Given the critical in vivo role of CD8+ T cell CRTAM-dependent dendritic cell binding, there may be therapeutic potential in blockade of CRTAM interactions. It is therefore of interest whether CRTAM might have ligands other than CADM1. We could demonstrate that a recombinant CRTAM-Fc protein bound to cells transfected with murine CADM1 isoforms (data not shown), confirming the reported CADM1–CRTAM interaction (2). Having generated Cadm1−/− animals (3), we were able to investigate Cadm1 dependency of CRTAM-Fc binding. Consistent with the model of Takeuchi et al., CRTAM-Fc binding was observed on CD11c+ dendritic cells (Fig. 1A) from wild-type animals, but not on those from Cadm1−/− animals (Fig. 1B). Specific CRTAM-Fc binding was not observed in any other splenic cell type (data not shown). Thus, the CRTAM–CADM1 interaction is nonredundant; and this, taken together with the data of Takeuchi et al., suggests its potential as a target for novel immunomodulatory agents. 1Takeuchi, A., Y. Itoh, A. Takumi, C. Ishihara, N. Arase, T. Yokosuka, H. Koseki, S. Yamasaki, Y. Takai, J. Miyoshi, et al. 2009. CRTAM confers late-stage activation of CD8+ T cells to regulate retention within lymph node. J. Immunol. 183: 4220–4228. 2Galibert, L., G. S. Diemer, Z. Liu, R. S. Johnson, J. L. Smith, T. Walzer, M. R. Comeau, C. T. Rauch, M. F. Wolfson, R. A. Sorensen, et al. 2005. Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule. J. Biol. Chem. 280: 21955–21964. 3.van der Weyden, L., M. J. Arends, O. E. Chausiaux, P. J. Ellis, U. C. Lange, M. A. Surani, N. Affara, Y. Murakami, D. J. Adams, A. Bradley. 2006. Loss of TSLC1 causes male infertility due to a defect at the spermatid stage of spermatogenesis. Mol. Cell. Biol. 26: 3595–3609.Abstract/FREE Full Text