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 IgG 1 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
StatePublished - Jan 1 2001

Fingerprint

CD40 Ligand
Transgenes
T-Lymphocytes
Lymph Nodes
Interleukin-2
Thymocytes
Humoral Immunity
Transgenic Mice
Antibody Formation
Immunoglobulin M
Immunoglobulins
B-Lymphocytes
Up-Regulation
Spleen
Immunoglobulin G

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.
Zhang, P. X. ; Cooper, E. ; Loomis, R. ; Flavell, R. A. ; Fuleihan, R. L. / Expression of a human CD40 ligand transgene in CD40 ligand-deficient mice. In: Transgenics. 2001 ; Vol. 3, No. 2-4. pp. 227-236.
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Zhang, PX, Cooper, E, Loomis, R, Flavell, RA & Fuleihan, RL 2001, 'Expression of a human CD40 ligand transgene in CD40 ligand-deficient mice', Transgenics, vol. 3, no. 2-4, pp. 227-236.

Expression of a human CD40 ligand transgene in CD40 ligand-deficient mice. / Zhang, P. X.; Cooper, E.; Loomis, R.; Flavell, R. A.; Fuleihan, R. L.

In: Transgenics, Vol. 3, No. 2-4, 01.01.2001, p. 227-236.

Research output: Contribution to journalArticle

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AU - Cooper, E.

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AU - Flavell, R. A.

AU - Fuleihan, R. L.

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N2 - 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 IgG 1 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.

AB - 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 IgG 1 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.

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Zhang PX, Cooper E, Loomis R, Flavell RA, Fuleihan RL. Expression of a human CD40 ligand transgene in CD40 ligand-deficient mice. Transgenics. 2001 Jan 1;3(2-4):227-236.