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

P. X. Zhang, E. Cooper, R. Loomis, R. A. Flavell, R. L. Fuleihan*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)227-236
Number of pages10
JournalTransgenics
Volume3
Issue number2-4
Publication statusPublished - Jan 1 2001

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Keywords

  • CD40 ligand
  • Cell surface molecules
  • Gene therapy
  • Immunodeficiency diseases
  • Knockout mice
  • T lymphocytes
  • Transgenic mice
  • X-linked hyper IgM

ASJC Scopus subject areas

  • Genetics

Cite this

Zhang, P. X., Cooper, E., Loomis, R., Flavell, R. A., & Fuleihan, R. L. (2001). Expression of a human CD40 ligand transgene in CD40 ligand-deficient mice. Transgenics, 3(2-4), 227-236.