Members of the T cell, Ig domain and mucin domain (Tim) family of proteins have recently been implicated in the control of T cell-mediated immune responses. Tim-1 (HUGO designation HAVCR1) polymorphisms have been linked to the regulation of atopy in mice and humans, suggestive of a role in immune regulation. Tim-1 is expressed upon activation of T cells. In concert with the increased expression of Tim-1, a binding partner for the extracellular domain of Tim-1 (eTim-1) was induced on activated T cells, and mRNA expression data was consistent with the binding partner being Tim-4. We found that co-immobilized recombinant eTim-1 was able to inhibit T cell activation mediated by CD3 + CD28 mAb. eTim-1 mediated its inhibitory effects on proliferation by arresting cell cycle at G(0)/G(1) phase through regulation of cell cycle proteins. In vivo, administration of eTim-1 proteins led to a decrease in both ear (contact hypersensitivity to oxazolone) and joint (methylated BSA antigen-induced arthritis) swelling. The inhibitory activity of eTim-1 in the T(h)1-dependent models was evidence that eTim-1 is able to modulate T cell responses. Manipulation of the Tim-1 interaction with its binding partner on T cells may therefore provide a novel target for therapeutic intervention in T cell-mediated diseases.

La presente invention concerne des sequences d'acides nucleiques qui codent de nouveaux polypeptides. L'invention concerne egalement des polypeptides codes par ces sequences d'acides nucleiques et des anticorps qui se lient par immunospecificite a ces polypeptides, ainsi que des derives, des variantes, des mutants ou des fragments des nouveaux polypeptides, polynucleotides ou anticorps specifiques des polypeptides. L'invention concerne enfin des procedes therapeutiques, de diagnostic et de recherche destines au diagnostic, au traitement et a la prevention de troubles dans lesquels sont impliques l'un ou l'autre des proteines et acides nucleiques humains de l'invention.