The function of the oligodendrocyte is the ensheathment of axons with myelin in the central nervous system. Myelin basic protein (MBP) expression in oligodendrocyte cytoplasm is a prelude to the onset of myelination. Little is known regarding the regulatory signals that influence the development of oligodendrocytes and their progenitor cells. Interleukin-2 (IL-2), a molecularly cloned T-cell derived lumphokine, induces oligodendrocyte proliferation and maturation (enhanced expression of MBP). The precise biological role of IL-2 in the regulation of gliogenesis is unknown at this time. The proposed studies will investigate the cellular and molecular mechanisms by which IL-2 influences the development of oligodendrocytes and glial progenitor cells. To define the effect of IL-2 on oligodendrocytes, I will analyze how IL-2 modulates the expression of myelination-specific antigens at both the mRNA and protein level. The influence of IL-2 on glial progenitor cell development will be studied as these cells can differentiate into either astrocytes or oligodendrocytes depending on culture conditions. The role of IL-2 in regulating their proliferation and differentiation will be examined. Studies will be done to identify, quantitate, and characterize the receptor for IL-2 on glial cells. A binding asasy will determine the number and affinity of receptors, while characterization by biochemical means will allow for comparison with the lymphoid IL-2 receptor. Damage to oligodendrocytes and/or myelin leads to various pathological conditions typified by the demyelinating disease, multiple sclerosis (MS). The proliferative capacity of mature oligodendrocytes and precursor cells, and their ability to regulate responses to injury are of extreme importance in wound-healing events. Understanding the control of normal oligodendrocyte development by IL-2 will be of value in influencing the course of regeneration and remyelination in diseases such as MS.
