en
Scientific article
English

CD4+CD25+ T cell-dependent inhibition of autoimmunity in transgenic mice overexpressing human Bcl-2 in T lymphocytes

Published inThe Journal of immunology, vol. 178, no. 5, p. 2778-2786
Publication date2007
Abstract

Regulation of lymphocyte survival is essential for the maintenance of lymphoid homeostasis preventing the development of autoimmune diseases. Recently, we described a systemic lupus erythematosus associated with an IgA nephropathy in autoimmune-prone (NZW x C57BL/6)F(1) overexpressing human Bcl-2 (hBcl-2) in B cells (transgenic (Tg) 1). In the present study, we analyze in detail a second line of hBcl-2 Tg mice overexpressing the transgene in all B cells and in a fraction of CD4(+) and CD8(+) T cells (Tg2). We demonstrate here that the overexpression of hBcl-2 in T cells observed in Tg2 mice is associated with a resistance to the development of lupus disease and collagen type II-induced arthritis in both (NZW x C57BL/6)F(1) and (DBA/1 x C57BL/6)F(1) Tg2 mice, respectively. The disease-protective effect observed in autoimmune-prone Tg2 mice is accompanied by an increase of peripheral CD4(+)CD25(+) hBcl-2(+) regulatory T cells (T(regs)), expressing glucocorticoid-induced TNFR, CTLA-4, and FoxP3. Furthermore, the in vivo depletion of CD4(+)CD25(+) T(regs) in (DBA/1 x C57BL/6)F(1) Tg2 mice promotes the development of a severe collagen type II-induced arthritis. Taken together, our results indicate that the overexpression of hBcl-2 in CD4(+) T cells alters the homeostatic mechanisms controlling the number of CD4(+)CD25(+) T(regs) resulting in the inhibition of autoimmune diseases.

Keywords
  • Animals
  • Arthritis, Experimental/*immunology/pathology
  • Autoimmune Diseases/chemically induced/*immunology/pathology
  • *Autoimmunity/genetics
  • B-Lymphocytes/immunology/pathology
  • Biological Markers
  • CD8-Positive T-Lymphocytes/immunology/pathology
  • Collagen Type II/toxicity
  • Gene Expression
  • Homeostasis/immunology
  • Humans
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2/genetics/*immunology
  • T-Lymphocytes, Regulatory/*immunology/pathology
Affiliation Not a UNIGE publication
Citation (ISO format)
GONZALEZ, Jovanna et al. CD4+CD25+ T cell-dependent inhibition of autoimmunity in transgenic mice overexpressing human Bcl-2 in T lymphocytes. In: The Journal of immunology, 2007, vol. 178, n° 5, p. 2778–2786.
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0022-1767
519views
0downloads

Technical informations

Creation08/27/2010 1:34:37 PM
First validation08/27/2010 1:34:37 PM
Update time03/14/2023 4:03:26 PM
Status update03/14/2023 4:03:26 PM
Last indexation02/12/2024 7:17:25 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack