Inhibition of in vitro and in vivo T cell responses by recombinant human Tim-1 extracellular domain proteins

Mehdi Mesri, Glennda Smithson, Ashwini Ghatpande, Andrei Chapoval, Suresh Shenoy, Ferenc Boldog, Craig Hackett, Carol E. Pena, Catherine Burgess, Alison Bendele, Richard A. Shimkets, Gary C. Starling

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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 G0/G1 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 Th1-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.

Original languageEnglish (US)
Pages (from-to)473-484
Number of pages12
JournalInternational Immunology
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Arthritis
  • Co-stimulation
  • DTH
  • HAVcr1
  • Proliferation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mesri, M., Smithson, G., Ghatpande, A., Chapoval, A., Shenoy, S., Boldog, F., Hackett, C., Pena, C. E., Burgess, C., Bendele, A., Shimkets, R. A., & Starling, G. C. (2006). Inhibition of in vitro and in vivo T cell responses by recombinant human Tim-1 extracellular domain proteins. International Immunology, 18(3), 473-484. https://doi.org/10.1093/intimm/dxh388