Characterization and role in experimental systemic lupus erythematosus of T‐cell lines specific to peptides based on complementarity‐determining region‐1 and complementarity‐determining region‐3 of a pathogenic anti‐DNA monoclonal antibody

Brosh, Naama; Eilat, Eran; Zinger, Heidy; Mozes, Edna

doi:10.1046/j.1365-2567.2000.00957.x

Cited by 22 publications

(21 citation statements)

References 24 publications

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“…Several groups have reported evidence in support of receptor presentation in autoimmunity (27,30,31,(35)(36)(37)(38)(39)(40). In a preceding study, we conducted a genealogical analysis of somatic mutations within an autoreactive B cell lineage obtained from a spontaneously diseased SNF 1 mouse.…”

Section: T Cell Tolerance To Germline-encoded Antibody Sequences In Amentioning

confidence: 99%

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

Guo

Smith

Guth

et al. 2005

The Journal of Immunology

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The BCR V region has been implicated as a potential avenue of T cell help for autoreactive B cells in systemic lupus erythematosus. In principle, either germline-encoded or somatically generated sequences could function as targets of such help. Preceding studies have indicated that class II MHC-restricted T cells in normal mice attain a state tolerance to germline-encoded Ab diversity. In this study, we tested whether this tolerance is intact in systemic lupus erythematosus-prone (New Zealand Black × SWR)F1 mice (SNF1). Using a hybridoma sampling approach, we found that SNF1 T cells were tolerant to germline-encoded Ab sequences. Specifically, they were tolerant to germline-encoded sequences derived from a lupus anti-chromatin Ab that arose spontaneously in this strain. This was true both for diseased and prediseased mice. Thus, there does not appear to be a global defect in T cell tolerance to Ab V regions in this autoimmune-prone strain either before or during autoimmune disease.

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Section: T Cell Tolerance To Germline-encoded Antibody Sequences In Amentioning

confidence: 99%

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

Guo

Smith

Guth

et al. 2005

The Journal of Immunology

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“…Autoreactive, anti-V H , Th cells that recognize peptides processed from the V H of anti-DNA Ig molecules (4,20,(22)(23)(24)(25)(26)(27) arise spontaneously in humans and mice with systemic lupus erythematosus (6,20,28) and modulate the development and progression of disease in lupus mice (4,6,20,29,30). These MHC class II-restricted, anti-V H Th cells increase anti-DNA Ab production by BWF 1 B cells (15).…”

Section: Plus B)mentioning

confidence: 99%

Induction of Autoantibody Production Is Limited in Nonautoimmune Mice

Singh

Ebling

Albuquerque

et al. 2002

The Journal of Immunology

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Many individuals develop a single or a few brief episodes of autoimmunity from which they recover. Mechanisms that quell pathologic autoimmunity following such a breakdown of self-tolerance are not clearly understood. In this study, we show that in nonautoimmune mice, dsDNA-specific autoreactive B cells exist but remain inactive. This state of inactivation in dsDNA-specific B cells could be disrupted by autoreactive Th cells; in this case T cells that react with peptides from the VH region of anti-DNA Abs (hereafter called anti-VH T cells). Immunization with anti-DNA mAb, its γ-chain or peptides derived from its VH region induced anti-VH Th cells, IgG anti-dsDNA Ab, and proteinuria. The breakdown of B cell tolerance in nonautoimmune mice, however, was short-lived: anti-DNA Ab and nephritis subsided despite subsequent immunizations. The recovery from autoimmunity temporally correlated with the appearance of T cells that inhibited anti-DNA Ab production. Such inhibitory T cells secreted TGFβ; the inhibition of anti-DNA Ab production by these cells was partly abolished by anti-TGFβ Ab. Even without immunization, nonautoimmune mice possess T cells that can inhibit autoantibody production. Thus, inhibitory T cells in nonautoimmune mice may normally inhibit T-dependent activation of autoreactive B cells and/or reverse such activation following stimulation by Th cells. The induction of such inhibitory T cells may play a role in protecting nonautoimmune mice from developing chronic autoimmunity.

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“…BALB/c mice were chosen to establish the SLE model due to their high response to the immunogen [4,30]. Female BALB/c mice, aged 5-6 weeks, were purchased from the Guangdong Laboratory Animal Center (Guangdong, China).…”

Section: Induction Of Experimental Sle In Balb/c Micementioning

confidence: 99%

“…5 , 3×10 4 , 1×10 4 and 0 hUCMSCs per 10 g body weight, respectively. Another 10 mice treated with saline were used as a negative control (NC) and were not transplanted with hUCMSCs.…”

Section: Hucmscs Transplantationmentioning

confidence: 99%

“…In both human SLE and murine lupus models, such as MRL/lpr and NZB/W (F1), the kidney is the major site of injury and immune complex formation and/or deposition [4]. The conventional treatment of SLE mainly relies on high doses of cyclophosphamide (CYC), glucocorticoids, mycophenolate mofetil (MMF), and other immunosuppressive and biological agents.…”

Section: Introductionmentioning

confidence: 99%

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Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

Li¹,

Ju²,

Zhou³

et al. 2015

Stud Stem Cells Res Ther

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Despite considerable advances in the treatment for systemic lupus erythematosus (SLE), there is still an unmet need to develop novel therapeutic approaches with improved efficacy and lower side effects. Here we explore human umbilical cord-derived mesenchymal stem cells (hUCMSCs) as a promising treatment for SLE induced by concanavalin A-activated spleno-lymphocyte in BALB/c mice. The isolated hUCMSCs, carrying specific MSC cell surface markers (CD105, CD73 and CD90), exhibited the potential to differentiate into osteogenic and adipogenic lineages. In mice with SLE, transplantation of hUCMSCs improved disease symptoms by decreasing the levels of serum autoantibody (antidsDNA and anti-nuclear) and cytokines (TNF-α and IFN-γ). The cell therapy significantly alleviated renal lesions by lowering serum urea nitrogen, creatine and uric acid, and increasing albumin. Using immunohistochemical staining, we found that that hUCMSCs decreased endocapillary hypercellularity, glomerular degeneration, and complement C3 immune complex deposition in the kidney. Mechanically, the therapy with hUCMSCs decreased CD4+/CD8+ cell ratio in animals. These data suggest that hUCMSCs may modulate autoimmunity in SLE mice by rebalancing CD4+/CD8+ cell population. Transplantation of hUCMSCs may be explored as a promising alternative approach in the treatment of human lupus.

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Characterization and role in experimental systemic lupus erythematosus of T‐cell lines specific to peptides based on complementarity‐determining region‐1 and complementarity‐determining region‐3 of a pathogenic anti‐DNA monoclonal antibody

Cited by 22 publications

References 24 publications

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

Induction of Autoantibody Production Is Limited in Nonautoimmune Mice

Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

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