Abstract.:Introduction:Estrogen (E2) was shown to prevent experimental autoimmune encephalomyelitis (EAE) and to produce a novel population of regulatory CD45dimVLA-4+ cells. Although their appearance was dependent upon an elevated hormonal level, E2 was not required for their production, as they also were induced by immunization with Mycobacterium tuberculosis as a component of complete Freund’s adjuvant.Materials and Methods:Molecular techniques, including ribonuclease protection assays and quantitative RT-PCR, were used to provide further characterization of CD45dimVLA-4+ cells. Moreover, we determined the developmental requirements of the CD45dimVLA-4+ cells using genetically modified mice and extensive flow cytometry analysis.Results:Characterization of CD45dimVLA-4+ mRNA profile revealed highly elevated levels of CD16, CD44, CCR3, IP-15, and IL-13 transcripts compared with their CD45highVLA-4+ counterparts. Furthermore, we found up-regulation of anti-apoptotic bcl-w and bcl-xl genes and transcripts encoding the TCRα and CD8α homodimer. The production of CD45dimVLA-4+ cells was evident in nude mice and in MHC class II- and β2-microglobulin, but not in CD1-deficient mice, suggesting a crucial role for CD1 in their induction.Conclusions:These findings suggest that CD45dimVLA-4+ cells might resemble natural killer T cells and imply possible roles for IL-13 and IP-15 in the protective function of CD45dimVLA-4+ cells. A better understanding of how these cells, also occurring naturally during pregnancy, suppress the harmful immune response of EAE may lead to novel therapeutic approaches to combat multiple sclerosis and other autoimmune diseases.