Effect of Long-Term Anti-CD4 or Anti-CD8 Treatment on the Development of lpr CD4 − CD8 − Double Negative T Cells and of the Autoimmune Syndrome in MRL- lpr / lpr Mice

Merino, Ramón; Fossati, Liliane; Iwamoto, Masahiro; Takahashi, Satoru; Lemoine, Robert; Ibnou-Zekri, Nabila; Pugliatti, L.; Merino, Jesús; Izui, Shozo

doi:10.1006/jaut.1995.0003

Cited by 40 publications

(34 citation statements)

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“…(NZW×B6)F1 mice were treated from birth (during the first 24 h of life) to 4 months of age with rat anti-CD4 mAb (GK-1.5), as described previously [38]. The efficiency of CD4 + T cell depletion was evaluated monthly by flow cytometry analysis of peripheral blood lymphocytes.…”

Section: Depletion Of Cd4 + T Cells In Vivomentioning

confidence: 99%

Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production

et al. 2004

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The presence of rheumatoid factors (RF) is a characteristic feature of patients with rheumatoid arthritis, but not systemic lupus erythematosus. In this study, we have explored the role of the anti-apoptotic Bcl-2 protein and the Y-linked autoimmune acceleration (Yaa) mutation in the production of IgG RF in comparison with IgG anti-DNA autoimmune responses. Analysis in C57BL/6 mice, in their F1 hybrids with lupus-prone NZW mice, and in bone marrow chimeras containing mixtures of C57BL/6 bcl-2-transgenic and BXSB non-transgenic cells demonstrated that an enforced Bcl-2 expression in B cells promoted the induction of IgG anti-DNA production in these mice, while significant IgG RF responses were observed only in mice developing high levels of gp70-anti-gp70 immune complexes and lethal glomerulonephritis. Moreover, in contrast to a synergistic interaction between the Yaa mutation and Bcl-2 overexpression on IgG anti-DNA production, the Yaa mutation failed to enhance the production of IgG RF induced in bcl-2-transgenic mice. Our results reveal that defects in the regulation of B cell apoptosis play a critical role in the production of IgG RF, and that the Yaa mutation differentially modulates RF and anti-DNA autoimmune responses, likely related to the nature of autoantigens involved in each autoimmune response.

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Section: Depletion Of Cd4 + T Cells In Vivomentioning

confidence: 99%

Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production

et al. 2004

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“…It is now well established that the lpr or Yaa gene-mediated acceleration of lupus-like autoimmune disease is dependent on the presence of CD4 ϩ T cells (5)(6)(7)(8)(9). However, the respective roles of two different T helper cell subsets, Th1 and Th2, exhibiting different capacities of cytokine secretion, in the development and acceleration of SLE have not yet been well defined.…”

Section: Introductionmentioning

confidence: 99%

Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice.

Takahashi¹,

Fossati²,

Iwamoto³

et al. 1996

J. Clin. Invest.

244

177

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“…Although mostly double-negative T cells accumulate in MRL/lpr mice, the initiation and progression of lupus disease in these mice were previously shown to be stringently dependent on CD4ϩ T cells (3,4). Murine CD4ϩ T cells can be induced to differentiate toward Th1, Th2, and recently defined Th17 phenotypes, according to the local cytokine milieu (5).…”

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confidence: 99%

Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses

Hou¹,

He²,

Li³

et al. 2011

Arthritis & Rheumatism

106

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Objective. SM934, an artemisinin derivative, possesses potent antiproliferative and antiinflammatory properties. The aim of this study was to examine the effects and explore the mechanisms of SM934 to treat autoimmune disease in lupus-prone female MRL/lpr mice.Methods. In vitro, the effects of SM934 on the activation of polyclonal CD4؉ T cells and the differentiation of naive CD4؉ T cells were examined. In vivo, the preventative or therapeutic effects of SM934 in MRL/lpr mice were investigated. Ex vivo, the mechanisms of treatment were explored according to the immunologic correlates of disease.Results In female MRL/lpr mice, an autoimmune syndrome develops spontaneously that closely resembles human systemic lupus erythematosus (SLE) and is characterized by the production of various autoantibodies and the development of fatal glomerulonephritis (1,2).Disease begins as early as 8 weeks of age in these mice, with the presence of detectable serum autoantibodies. Pronounced lymphadenopathy is observed at 12 weeks of age, which is largely attributable to the accumulation of a population of B220ϩ and CD3ϩ cells that are mostly CD4Ϫ and CD8Ϫ (double-negative T cells). By 12-16 weeks of age, MRL/lpr mice begin to produce a variety of autoantibodies, including antidouble-stranded DNA (anti-dsDNA) antibodies. Multiple organs are affected, and a steady deterioration of renal function manifesting as severe proteinuria begins at approximately 16 weeks of age. From 16 weeks of age to 24 weeks of age, proliferative immune complex-

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Effect of Long-Term Anti-CD4 or Anti-CD8 Treatment on the Development of lpr CD4 − CD8 − Double Negative T Cells and of the Autoimmune Syndrome in MRL- lpr / lpr Mice

Cited by 40 publications

References 0 publications

Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production

Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production

Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice.

Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses

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