IngentaConnect A pivotal role of cell-bound but not soluble CD4 molecules in ful...

Authors: Zhang, Y.¹; Yasuda, T.¹; Wang, C. R.²; Yoshimoto, T.²; Nagase, H.³; Takamoto, M.³; Tsubura, A.⁴; Kimura, M.⁵; Matsuzawa, A.¹

Source: Clinical & Experimental Immunology, Volume 122, Number 1, October 2000 , pp. 124-132(9)

Publisher: Blackwell Publishing

Abstract:

The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL-Fas^lprcg/Fas^lprcg (MRL-lpr^cg) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL-lpr^cg mice homozygous (CD4^slpr^cg), heterozygous (CD4^s/mlpr^cg), and wild-type (CD4^mlpr^cg) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4^slpr^cg compared with CD4^mlpr^cg and CD4^s/mlpr^cg mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti-nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE-like manifestations, and suggest that CD4⁺ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220⁺CD4⁻CD8⁻ (double-negative (DN)) T cells in CD4^slpr^cg mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4^slpr^cg than CD4^mlpr^cg mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.

Keywords: lupus nephritis; autoimmunity; MRL-Faslprcg mice; CD4 molecules

Document Type: Research article

DOI: 10.1046/j.1365-2249.2000.01347.x

Affiliations: 1: Laboratory Animal Research Centre, and Departments of 2: Allergology and 3: Department of Parasitology, Shinshu University School of Medicine, Matsumoto, and 4: Department of Pathology, Kansai Medical University, Osaka, Japan 5: Internal Medicine, Institute of Medical Science, University of Tokyo and

You have access to the full text article on a website external to Ingentaconnect.

Please click here to view this article on InterScience.

You may be required to register and activate access on InterScience before you can obtain the full text. If you have any queries please contact onlinehelp@oxon.blackwellpublishing.com

A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Faslprcg/Faslprcg mice

A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Fas^lprcg/Fas^lprcg mice