The Role of Histone 3 Lysine 4 Methyltransferase Kmt2d in T cell Homeostasis

KMT2D is a methyltransferase that adds a methyl group to histone H3 lysine 4 (H3K4). This epigenetic modification promotes gene expression and plays an important role in the differentiation and development of immune cells. We previously found that mice whose T cells are deficient for KMT2D display reduced populations of CD4+ and CD8+ T cells when compared to wildtype mice. We hypothesized this lowered T cell count was the result of reduced homeostatic proliferation in KMT2D knockout mice, which is the process by which cells repopulate to resolve lymphopenia. We assessed proliferation in mutant mice by staining for apoptotic and proliferation markers to determine the cause of the observed lymphopenia. Through this analysis, we found that KMT2D deficient T cells actually exhibit reduced apoptosis and increased expression of proliferative markers when compared to wildtype mice. To directly compare homeostatic proliferation between deficient and wildtype T cells, both populations were transferred into lymphopenic hosts and allowed to divide for seven days. Proliferation was assessed using CFSE staining and KMT2D deficient T cells were found to have divided less than wildtype mice, indicating that KMT2D promotes proliferation in T cells. Additional research is needed to determine the mechanics of KMT2D’s impact on T cell maintenance to explain why KMT2D-TCD mice are unable to resolve lymphopenia.Bachelor of Scienc