Glucocorticoid-Induced TNFR family Related gene (GITR), a Tumor Necrosis Factor Receptor Superfamily (TNFRSF) member involved in immune/inflammatory processes, has been previously shown to regulate T cell activation. To study GITR role in antigen presenting cells, we evaluated the capability of bone marrow derived dendritic cells (BMDC) from GITR -/- mice to stimulate the activation of CD4 +CD25 - T lymphocytes. We found that GITR -/- BMDC are weaker stimulators of T cell proliferation than GITR +/+ BMDC, either in syngenic or allogenic BMDC/T cell co-cultures. Expression of GITR in GITR -/- BMDC restored their ability to activate T cells while GITR silencing in GITR +/+ BMDC inhibited the capability to stimulate T cells. GITR -/- BMDC showed a reduced production of the pro-inflammatory cytokine IL-6 and an increased production of the anti-inflammatory cytokine IL-10. Notably, co-culture of CD4 +CD25 - cells with GITR -/- BMDC originated FoxP3 + cells, secreting IL-10 and TGF-β. Finally, in vivo injection of GITR -/- OVA-loaded BMDC led to a lower cell number and a lower activated cell number in draining lymph nodes than in GITR +/+ OVA-loaded BMDC injected mice. Together, these results indicate that GITR plays a role in regulating BMDC activity. © 2010 Elsevier B.V.

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