Methods for blocking autoreactive T cell-initiated destruction of tissues in a mammal are provided. In one embodiment, the method comprises administering a purified CD24 polypeptide, a fusion protein comprising such polypeptide, or a biologically active fragment of such polypeptide to a mammalian subject who is suspected of having or predisposed to having an autoimmune disease. In another embodiment, anti-CD24 antibody or anti-CD24 Fab fragments are administered to the subject. In another embodiment, the method comprises administering a CD24 antisense molecule, an expression vector encoding a CD24 antisense molecule, CD24 dsRNAi, or an expression vector encoding CD24 dsRNAi to the subject. The present invention also relates to isolated and purified CD24 fusion proteins employed in the present methods and to transgenic mice that express the human CD24 protein on their T cells and/or their vascular endothelial cells but do not express murine heat shock antigen on any cells.
