CD24 in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis: Targeting Redundancy for Immunotherapy?

An interesting puzzle in the field of T cell costimulation is the apparent redundancy of costimulatory molecules for T cell activation. Our analysis over the last decade of CD24 may shed some light on the issue. CD24 was first identified as a costimulatory molecule for T cell activation over 12 years ago when we used activated B cells as antigen-presenting cells. Subsequent studies using mice with a targeted mutation of CD24 revealed that CD24 has an overlapping function with CD28 although it is dispensable for T cell activation in the lymphoid organs. Surprisingly, mice with a targeted mutation of CD24 are completely resistant to experimental autoimmune encephalomyelitis (EAE). Both T cells and non-T host cells must express CD24 in order to develop EAE. CD24 expression on non-T cells controls the local expansion of the pathogenic T cells in the central nervous system (CNS), while T cell expression of the CD24 gene is essential for homeostatic proliferation of T cells in a lymphopenic environment. The significance of CD24 in human autoimmune diseases is highlighted by the discovery that CD24 polymorphism is a genetic modifier for the risk and progression of multiple sclerosis. Thus, a costimulatory molecule redundant in the lymphoid organ can be essential for immune response in target organs. This type of costimulatory molecules is an ideal target for immunotherapy of the autoimmune diseases.