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. 2005 Nov;73(11):7502–7508. doi: 10.1128/IAI.73.11.7502-7508.2005

FIG. 6.

FIG. 6.

Hypothetical mechanisms by which GITR lack promotes a more efficient clearance of C. albicans. In panel A, the low level of IL-12 observed following T-cell receptor stimulation by C. albicans antigens (Ags) in the presence of GITR/GITRL signaling may be explained by three (1, 2, and 3) concurrent intracellular pathways activated following binding of GITRL (expressed on antigen presenting cells) with GITR (expressed at high levels in Treg and activated T cells). IL-12 and other ligands (Ls), including other cytokines (Cks), activate the respective receptors (IL-12R and other R's) either in antigen-presenting cells or in activated CD4+ T cells, skewing to Th2 cytokine production. Also, activation of GITR in activated CD4+ cells (4) might play a role. In panel B, the lack of GITR causes a lack of both GITR and GITRL signaling, high IL-12 levels, and cytokine production promoting a prevalent Th1 polarization. The high efficiency of C. albicans clearance in GITR−/− mice might be obtained in GITR+/+ mice using antibodies or fusion proteins with antagonist function.