Induction of Functional Interleukin-2 Receptor in Mouse Microglia

Abstract: Interleukin (IL)-2, initially discovered for its mitogenic activity on T cells, also acts on monocytes, resulting in the activation of cytokine production, superoxide production, and tumoricidal activity. Because severe brain damage was observed in IL-2-transgenic mice, this cytokine may have some influence(s) on the cells of the CNS. We investigated IL-2 receptor-bearing cells in the CNS and found that activated microglia expressed α-chain mRNA and immunoreactive IL-2 receptor β-chain protein in culture. Although microglia did not express IL-2 receptors under normal culture conditions, they were induced to express these receptors by lipopolysaccharide (LPS) in a time-dependent manner. The IL-2 receptors were found to be functional because the viability and growth activity of LPS-treated microglia, but not untreated controls, increased in response to recombinant mouse IL-2 as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and bromodeoxyuridine uptake experiment, respectively. These effects of recombinant IL-2 were blocked by pretreatment with anti-mouse IL-2 receptor β-chain antibody. Our findings suggest that activated microglia in the CNS can respond to this T cell-derived factor regulating their growth, which may be an important mechanism of communication between nervous and immune systems in physiological and pathological conditions.