Endogenous retroviral sequences in the pathogenesis of systemic autoimmune disease

Walchner, M.

doi:10.1001/archderm.133.6.767

Cited by 7 publications

(8 citation statements)

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“…It is estimated that endogenous retroviral sequences (ERVs) make up at least 1% of total genomic DNA (8). ERVs may potentially affect the development and outcome of a retroviral infection (9 -11).…”

Section: Urine Aids (Maids)mentioning

confidence: 99%

Timed Ablation of Regulatory CD4+ T Cells Can Prevent Murine AIDS Progression

Beilharz

Sammels

Paun

et al. 2004

The Journal of Immunology

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We describe successful immunotherapy of murine AIDS (MAIDS) in C57BL/6J mice based on the elimination of replicating CD4+ regulator T cells. We demonstrate that a single injection of the antimitotic drug vinblastine (Vb) given 14 days postinfection (p.i.) with LP-BM5 can prevent MAIDS progression. Treatment with anti-CD4 mAb at 14 days p.i. is similarly able to prevent MAIDS. Treatment at other time points with Vb or anti-CD4 mAb is ineffective. The effect is based on ablation of a replicating dominantly suppressive CD4+ T cell population, as indicated by adoptive transfer and in vivo depletion experiments using mAbs against CD4 as well as combinations of mAbs against the known regulatory cell surface markers CD25, GITR, and CTLA-4. Cell surface marker analysis shows a population of CD4+CD25+ cells arising shortly before day 14 p.i. Cytokine analyses show a peak in IL-10 production from day 12 to day 16 p.i. MAIDS-infected mice also have CD4+ T cells with significantly higher expression levels of CD38 and particularly CD69, which have been demonstrated to be regulator T cell markers in the Friend retroviral model. The immunotherapy appears to prevent disease progression, although no protection against reinfection with LP-BM5 is generated. These data define a new therapy for murine retroviral infection, which has potential for use in other diseases where T regulator cell-mediated immunosuppression plays a role in the disease process.

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Section: Urine Aids (Maids)mentioning

confidence: 99%

Timed Ablation of Regulatory CD4+ T Cells Can Prevent Murine AIDS Progression

Beilharz

Sammels

Paun

et al. 2004

The Journal of Immunology

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“…Recent data indicate that the classification of type 1 and 2 Th cells according to their cytokine profile may also be the case for CD8 þ T cell subsets [3][4][5][6]. Humoral immune defects are often found in clinical disorders with an autoimmunerelated background, retroviral infections or B cell malignancies such as myeloma and chronic B cell leukaemia (B-CLL) [7][8][9][10]. Reduction of polyclonal immunoglobulins found in these disorders may involve common pathogenic pathways, since autoimmune-related features are frequently observed in B-CLL patients, and patients with systemic autoimmune disease are more prone to developing malignant B cell disorders [8,9,11].…”

Section: Introductionmentioning

confidence: 99%

“…Humoral immune defects are often found in clinical disorders with an autoimmunerelated background, retroviral infections or B cell malignancies such as myeloma and chronic B cell leukaemia (B-CLL) [7][8][9][10]. Reduction of polyclonal immunoglobulins found in these disorders may involve common pathogenic pathways, since autoimmune-related features are frequently observed in B-CLL patients, and patients with systemic autoimmune disease are more prone to developing malignant B cell disorders [8,9,11]. Common immunological abnormalities are elevation of IL-6 and IL-10 levels as well as down-regulation of IFN-g [9,[12][13][14][15], indicating a lack of type 1 cytokines.…”

Section: Introductionmentioning

confidence: 99%

“…Reduction of polyclonal immunoglobulins found in these disorders may involve common pathogenic pathways, since autoimmune-related features are frequently observed in B-CLL patients, and patients with systemic autoimmune disease are more prone to developing malignant B cell disorders [8,9,11]. Common immunological abnormalities are elevation of IL-6 and IL-10 levels as well as down-regulation of IFN-g [9,[12][13][14][15], indicating a lack of type 1 cytokines. The involvement of CD4 þ T cells in the pathogenesis of humoral immune defects is well known, but recent data also pointed to an involvement of CD8 þ T cell subsets [6,7,9].…”

Section: Introductionmentioning

confidence: 99%

“…Common immunological abnormalities are elevation of IL-6 and IL-10 levels as well as down-regulation of IFN-g [9,[12][13][14][15], indicating a lack of type 1 cytokines. The involvement of CD4 þ T cells in the pathogenesis of humoral immune defects is well known, but recent data also pointed to an involvement of CD8 þ T cell subsets [6,7,9]. CD8 þ T cells were shown to suppress production of immunoglobulins in the absence of CD4 þ T helper cells and were thus able to interfere with the regulation of immunoglobulin production [16].…”

Section: Introductionmentioning

confidence: 99%

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Elevation of CD8+ CD11b+ Leu-8− T cells is associated with the humoral immunodeficiency in myeloma patients

Walchner

Wick

1997

Clinical and Experimental Immunology

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SUMMARYRecurrent bacterial infections due to humoral immunodeficiency are an important cause of death in myeloma patients. Recent data indicate that CD8 þ T lymphocytes and a reduction of T helper type 1 cells with disease progression may be involved in the regulation of polyclonal immunoglobulin secretion. In mixed lymphocyte cultures derived from peripheral blood mononuclear cells (PBMC) of 24 myeloma patients with reduced immunoglobulin serum levels we investigated the association of CD4 þ and CD8 þ T cell subsets and immunoglobulin-secreting B cells (ISC) upon mitogenic stimulation with pokeweed mitogen (PWM) and concanavalin A (Con A). In supernatants of cultured PBMC of myeloma patients the spontaneous secretion of the type 1 cytokine interferon-gamma was reduced. After PWM stimulation reduced numbers of polyclonal ISC were found in 79% of patients, and monoclonal ISC were observed in 12% of patients. After Con A stimulation, again formation of polyclonal ISC was reduced, but monoclonal ISC were found in 41% of patients. Elevation of monoclonal and reduction of polyclonal ISC after stimulation with Con A were associated with an increase of CD8 þ CD11b þ Leu-8 ¹ T cells (P < 0 . 05). We conclude that the elevated numbers of CD8 þ CD11b þ Leu-8 ¹ T cells play a role in the stimulation of monoclonal and suppression of polyclonal immunoglobulin secretion in myeloma patients.

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Lupus erythematodes

Meurer¹

Dermatologie Und Venerologie

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Endogenous retroviral sequences in the pathogenesis of systemic autoimmune disease

Cited by 7 publications

References 0 publications

Timed Ablation of Regulatory CD4+ T Cells Can Prevent Murine AIDS Progression

Timed Ablation of Regulatory CD4+ T Cells Can Prevent Murine AIDS Progression

Elevation of CD8+ CD11b+ Leu-8− T cells is associated with the humoral immunodeficiency in myeloma patients

Lupus erythematodes

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