Expression of a human CD40 ligand transgene in CD40 ligand-deficient mice

X-linked hyper IgM is a severe immune deficiency disease that results from defects in the CD40 ligand (CD40L) gene. We generated transgenic mice expressing human CD40L under the regulation of the IL-2 promoter to correct CD40L expression and function in CD40L-deficient mice. Tg⁺CD40L-deficient mice showed inducible expression of human CD40L on lymph node T cells but not on thymocytes or spleen T cells. However, serum immunoglobulin levels and T cell-dependent antibody responses were similar between Tg⁺ and Tg^- CD40L-deficient mice. Human CD40L expressed on the surface of lymph node T cells was functional because it induced up regulation of B7-2 expression and IgG₁ synthesis in CD40L-deficient mouse B cells in vitro. These results indicate that IL-2 promoter driven CD40L gene expression can correct CD40L expression in lymph node T cells but is not sufficient to correct in vivo humoral immunity.