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

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

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Division of Neonatology, Department of Pediatrics, University of California San Francisco, San Francisco, CA 94110, USA.


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.

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