Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration

Eur J Immunol. 2013 May;43(5):1208-19. doi: 10.1002/eji.201242730. Epub 2013 Mar 25.

Abstract

Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37(-/-) mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell-mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37(-/-) mice coincides with a striking failure to induce antigen-specific IFN-γ-secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemo-tactic migration; integrin-mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naïve T cells. In addition, multiphoton microscopy-based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37(-/-) mice. Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37(-/-) mice is impaired DC migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adoptive Transfer
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Cell Adhesion / immunology
  • Cell Movement / immunology*
  • Cell Proliferation
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Female
  • Gene Expression
  • Immunity, Cellular*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / pathology
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Neoplasm Transplantation
  • Skin / immunology
  • Skin / pathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Tetraspanins / deficiency
  • Tetraspanins / genetics
  • Tetraspanins / immunology*

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Cd37 protein, mouse
  • Tetraspanins
  • Interferon-gamma