The Role of Interleukin-10 in the Generation of CD4+ and CD8+ Memory T Cells (Expressing a CD44+, CD62L– Phenotype) and Their Contribution to the Regulation of Immunoglobulin E Antibody Formation

Abstract

Background: Immunization of mice with low doses of protein antigens like keyhole limpet hemocyanin (KLH) results in high immunoglobulin (Ig) E Ab titers in the sera of those mice while the application of high doses leads to the production of only marginal amounts of IgE but high levels of IgG2a and IgG1 antibodies. The aim of these studies is to elucidate the role of interleukin-10 (IL-10) in the generation of memory T cells and their contribution to the production of IgE Ab. Methods: Both IL-10-deficient mice and control mice were immunized repeatedly with KLH. Serum levels of KLH-specific Ab were measured. The frequencies of memory T cells were determined by flow cytometry and the role of CD4+ and CD8+ T cells was evaluated. Results: IL-10-deficient mice show an augmented production of IgE in vivo. They exhibit enhanced ratios of CD4+:CD8+ memory T cells with a CD44+, CD62L– phenotype with a significantly raised generation of CD4+ memory T cells. On the other hand, the development of CD8+ memory T cells is reduced moderately in IL-10-deficient mice, which is an interesting fact since it has been shown that primed CD8+ T cells suppress IgE Ab production at least in vitro. The ratios of total CD4+:CD8+ T cells are augmented in IL-10-deficient mice compared to wild-type mice and in K01 mice compared to K100 mice in vivo. Conclusions: The elevated ratios of CD4+:CD8+ T cells indicate a higher capacity to provide B cell help, which results in a strongly elevated IgE response in IL-10-deficient mice. These altered ratios are furthermore interesting in view of the regulatory role of CD8+ T cells which provide a suppressive potential regarding IgE Ab production as shown in vitro. The capacity of IL-10 to suppress IgE Ab production by reduction of the CD4+:CD8+ memory T cell ratio opens new possibilities in the interference with allergic disorders.