Naive human T cells are activated and proliferate in response to the heme oxygenase-1 inhibitor tin mesoporphyrin

J Immunol. 2010 Nov 1;185(9):5279-88. doi: 10.4049/jimmunol.0903127. Epub 2010 Oct 4.

Abstract

Heme oxygenase-1 (HO-1) and its catabolic by-products have potent anti-inflammatory activity in many models of disease. It is not known, however, if HO-1 also plays a role in the homeostatic control of T cell activation and proliferation. We demonstrate here that the HO-1 inhibitor tin mesoporphyrin (SnMP) induces activation, proliferation, and maturation of naive CD4(+) and CD8(+) T cells via interactions with CD14(+) monocytes in vitro. This response is dependent upon interactions of T cells with MHC class I and II on the surface of CD14(+) monocytes. Furthermore, CD4(+)CD25(+)FoxP3(+) regulatory T cells were able to suppress this proliferation, even though their suppressive activity was itself impaired by SnMP. Given the magnitude of the Ag-independent T cell response induced by SnMP, we speculate that HO-1 plays an important role in dampening nonspecific T cell activation. Based on these findings, we propose a potential role for HO-1 in the control of naive T cell homeostatic proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Proliferation / drug effects
  • Cell Separation
  • Enzyme Inhibitors / pharmacology*
  • Flow Cytometry
  • Heme Oxygenase-1 / antagonists & inhibitors*
  • Heme Oxygenase-1 / immunology
  • Humans
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Metalloporphyrins / pharmacology*
  • Monocytes / immunology
  • Monocytes / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology

Substances

  • Enzyme Inhibitors
  • Lipopolysaccharide Receptors
  • Metalloporphyrins
  • tin mesoporphyrin
  • Heme Oxygenase-1