CD24 inhibits thymic deletion of myelin antigen-specific T cells (129.34)

Abstract

Abstract CD24 is a glycosylphosphatidylinositol (GPI) anchored cell surface glycoprotein that is expressed in hematopoietic cells and cells of the central nervous system (CNS). We have previously shown that CD24 is required for the induction of experimental autoimmune encephalomyelitis (EAE), an experimental model of human disease multiple sclerosis. In CD24−/− mice, normal levels of myelin oligodendrocyte glycoprotein (MOG) specific T cell were primed, however these T cells were non-pathogenic. To understand this issue, we bred CD24−/− mice with 2D2 TCR transgenic mice, which bear TCR specific to MOG, and generated 2D2 TCR transgenic mice with or without CD24. Here we show that 2D2 TCR transgenic mice with CD24-deficiency (2D2/CD24−/−) have remarkably withered thymus. In peripheral lymphoid organs, transgenic T cells from 2D2/CD24−/− mice have an immature phenotype (CD4−CD8−), do not respond to MOG peptide stimulation, and fail to cause autoimmune inflammation in the CNS and optical nerves. In contrast, OT-2 TCR transgenic mice with CD24 deficiency (OT-2/CD24−/−), which bear TCR specific to chicken ovalbumin (OVA), have normal thymus and their peripheral T cells have a normal response to OVA peptide. These data suggest that CD24 inhibits thymic deletion of myelin antigen, but not foreign antigen-reactive T cells.