A regulatory role for CD37 in T cell proliferation

J Immunol. 2004 Mar 1;172(5):2953-61. doi: 10.4049/jimmunol.172.5.2953.

Abstract

CD37 is a leukocyte-specific protein belonging to the tetraspanin superfamily. Previously thought to be predominantly a B cell molecule, CD37 is shown in this study to regulate T cell proliferation. CD37-deficient (CD37(-/-)) T cells were notably hyperproliferative in MLR, in response to Con A, or CD3-TCR engagement particularly in the absence of CD28 costimulation. Hyperproliferation was not due to differences in memory to naive T cell ratios in CD37(-/-) mice, apoptosis, or TCR down-modulation. Division cycle analyses revealed CD37(-/-) T cells to enter first division earlier than wild-type T cells. Importantly, proliferation of CD37(-/-) T cells was preceded by enhanced early IL-2 production. We hypothesized CD37 to be involved in TCR signaling and this was supported by the observation that CD4/CD8-associated p56(Lck) kinase activity was increased in CD37(-/-) T cells. Remarkably, CD37 cross-linking on human T cells transduced signals that led to complete inhibition of CD3-induced proliferation. In the presence of CD28 costimulation, CD37 engagement still significantly reduced proliferation. Taken together, these results demonstrate a regulatory role for CD37 in T cell proliferation by influencing early events of TCR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, CD / physiology*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Antigens, Neoplasm / physiology*
  • Apoptosis / genetics
  • Apoptosis / immunology
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / enzymology
  • Cell Division / genetics
  • Cell Division / immunology
  • Cell Separation
  • Cytokines / biosynthesis
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Glycoproteins / deficiency
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Glycoproteins / physiology*
  • Growth Inhibitors / immunology
  • Growth Inhibitors / metabolism
  • Humans
  • Immunologic Memory / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptor-CD3 Complex, Antigen, T-Cell / antagonists & inhibitors
  • Receptor-CD3 Complex, Antigen, T-Cell / biosynthesis
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / enzymology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Tetraspanins
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • CD37 protein, human
  • Cd37 protein, mouse
  • Cytokines
  • Glycoproteins
  • Growth Inhibitors
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Tetraspanins
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)