Production of IL-4 and expression of CD40 ligand by human CD8 T cells.

Abstract

The role of CD8(+) T cells in IgE synthesis remains unclear. The aim of this study was to investigate IL-4 production and CD40 ligand expression by human CD8(+) T cells. We conducted functional and phenotypic analyses of human T cells in peritoneal washings from severe combined immunodeficiency mice reconstituted with PBMCs from normal and atopic human donors. We also examined the expression of IL-4 and CD40 ligand by CD8(+) T cells from a patient with adenosine deaminase deficiency who received autologous T cell-directed gene therapy. Transfer of atopic cells into the mice caused production of IgE and IgG with increased expression of IL-4 and CD40 ligand mRNA. In addition, both intracellular IL-4 and cell surface CD40 ligand were detected in CD8(+) and in CD4(+) T cells. CD8(+) T-cell lines generated from the patient's T cells carrying the adenosine deaminase gene expressed not only IL-4 mRNA and protein but also CD40 ligand mRNA and protein after being stimulated with an anti-CD3 mAb. After anti-CD3 stimulation and paraformaldehyde fixation, CD8(+) T cells induced IgE synthesis by normal human B cells in the presence of recombinant IL-4. Taken together, these results demonstrate that IL-4-producing and CD40 ligand-expressing CD8(+) cells are detectable among human T cells and suggest that such cells may promote IgE production by B cells under some conditions.