Selective Depression of the Xenogeneic Cell-Mediated Lympholysis in Systemic Lupus Erythematosus

Charpentier, B; Carnaud, Claude; Bach, Jean-Marie

doi:10.1172/jci109469

Cited by 27 publications

(3 citation statements)

References 44 publications

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“…A substantial component of systemic autoimmune disease such as lupus involves the breakdown of lymphocyte tolerance, primarily through the expansion of autoreactive CD4 + T cells that provide help to B cells, which can in turn produce autoantibodies with various specificities (1). Although comparatively less is understood about how CD8 + T cells contribute to disease progression, perturbations in CTL function are evident in lupus patients (2,3). Several groups, including ours, have now shown that a functionally competent CD8 + T cell compartment is required to restrict disease severity in lupus-prone mice (4)(5)(6)(7), and subsets of CD8 + T cells have been identified that can suppress excessive CD4 + T follicular helper cell help to B cells, which is essential for maintenance of self tolerance (8).…”

Section: Introductionmentioning

confidence: 99%

Strong Selection of a Few Dominant CD8 Clones in a TLR7-Dependent Autoimmune Mouse Model

Morawski

Bolland

2019

ImmunoHorizons

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Systemic lupus is characterized by the expansion of a self-reactive repertoire of B cells and CD4 cells that together promote IgG Ab production against common nuclear Ags. Although several studies have suggested roles for CD8+ T cells in lupus, the full contribution of these lymphocytes to disease remains undefined. In particular, few studies have examined TCR clonotypes of the CD8 pool in lupus. We previously described activated but nonpathogenic CD8+ T cells in a mouse model of systemic autoimmune disease triggered by increased copy number of the tlr7 gene (TLR7tg mice), in which some of these T cells accumulate in the brain. In this article, we report, through the analysis of TCRβ sequences, that CD8 cells from TLR7tg animals are strongly selected for a small number of clones, some of them reaching 30% of the repertoire, compared with less than 0.4% for the top clone in any wild type mice. High frequency clones are variable in sequence among individual TLR7tg mice and are distinct from top clones in the control animals, whereas CDR3 sequences of spleen and brain-resident T cells from the same TLR7tg animals have perfect concordance. These results suggest that top CD8 clones are selected in stochastic fashion in each animal but limit further diversification, and that brain-infiltrating CD8 cells in TLR7tg mice are not selected by a common tissue Ag. This kind of extreme clonal dominance and narrowing of the CD8+ repertoire might impair anti-viral responses and should be considered as an additional detrimental feature of chronic autoimmune disease.

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Section: Introductionmentioning

confidence: 99%

Strong Selection of a Few Dominant CD8 Clones in a TLR7-Dependent Autoimmune Mouse Model

Morawski

Bolland

2019

ImmunoHorizons

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“…Although the defects partially resolved with disease remission, a residual disorder persisted. The coexistence of this abnormal T cell membrane function with other discrete T cell dysfunctions (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) …”

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confidence: 99%

Impaired T cell capping and receptor regeneration in active systemic lupus erythematosus. Evidence for a disorder intrinsic to the T lymphocyte.

Kammer¹

1983

J. Clin. Invest.

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“…[20][21][22] Additional serum factors such as antilymphocyte antibodies to surface antigens 23,24 could as well inhibit T-cell proliferative responses 25,26 or T-cell cytotoxic activities. 27…”

Section: T-cell Function In Slementioning

confidence: 99%

Lupus and T Cells

Cava

2009

Lupus

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T-cell abnormalities and aberrant T helper cytokine profiles have been implicated in the loss of immune tolerance to nuclear and cytoplasmic antigens and linked to a variety of clinical manifestations in systemic lupus erythematosus (SLE). Here, we review the role of T cells in promoting and maintaining SLE in relation to their cellular and molecular abnormalities and provide an update on recent T cell-targeted therapeutic approaches for the restoration of T cell homeostasis in the disease.

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Selective Depression of the Xenogeneic Cell-Mediated Lympholysis in Systemic Lupus Erythematosus

Abstract: A B S T R A C

Cited by 27 publications

References 44 publications

Strong Selection of a Few Dominant CD8 Clones in a TLR7-Dependent Autoimmune Mouse Model

Strong Selection of a Few Dominant CD8 Clones in a TLR7-Dependent Autoimmune Mouse Model

Impaired T cell capping and receptor regeneration in active systemic lupus erythematosus. Evidence for a disorder intrinsic to the T lymphocyte.

Lupus and T Cells

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