Abstract
The glucocorticoid‐induced TNF‐related receptor (GITR) and its natural ligand (GITRL) belong to the TNF receptor and TNF superfamilies (TNFRSF18 and TNFSF18). The expression profile of both GITR and GITRL suggests that they play primary roles in the immune response. To better understand the role of GITR/GITRL interactions in the mouse immune system, we generated transgenic GITRL mice under the control of a MHC class II promoter. Elevated expression of GITRL was observed on macrophages, dendritic cells and B cells. GITRL transgenic mice had mild microcytic anemia and substantially enlarged spleens. Histologically, these animals exhibited multi‐organ lymphocytic infiltrates which were particularly profound in the spleen, lung, liver, kidneys, and salivary glands. Immunophenotyping of these animals demonstrated higher percentages and numbers of T and B cells in spleens and other lymphoid organs. Germinal center formation was rare in the lymphoid organs. The percentage of total splenic CD4+ T cells in transgenic mice was elevated while the total CD8+ T cell percentage was diminished compared to WT littermates. Interestingly, the percentage of CD4+ FOXP3+ cells in the spleen was greatly increased but very few of these cells were positive for GITR surface expression. In conclusion, enhanced expression of GITRL on MHC class II positive mouse cells leads to expansion of both T and B cell compartments and lymphoid organ enlargement. Further evaluation of T cell subsets and the consequences of enhanced GITR/GITRL interactions in these animals is ongoing.
Published Version
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