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

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2010-11, Vol.185 (9), p.5279-5288
Main Authors: Burt, Trevor D, Seu, Lillian, Mold, Jeffrey E, Kappas, Attallah, McCune, Joseph M
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0903127