Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4+ T cells in healthy individuals

Nielsen, Claus Henrik; Leslie, R. G. Q.; Jepsen, Birgit; Kazatchkine, Michel D.; Kaveri, Srini V.; Fischer, Elizabeth

doi:10.1002/1521-4141(200109)31:9<2660::aid-immu2660>3.0.co;2-e

Cited by 56 publications

(52 citation statements)

References 41 publications

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“…27 In brief, the CFSE content of the 1 Positive CD4 + T-cell proliferation (net proliferation > 1%). 2 Human leucocyte antigen (HLA) typing was carried out in-house using low-resolution technology.…”

Section: Measurement Of Cd4mentioning

confidence: 99%

T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

et al. 2008

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SummaryAutoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and related the patient responses to disease activity, as indicated by magnetic resonance imaging. The MBP induced a dose-dependent release of interferon-c (IFN-c), tumour necrosis factor-a (TNF-a) and interleukin-10 (IL-10) by patient-derived MNCs. The patients' cells produced higher amounts of IFN-c and TNF-a, and lower amounts of IL-10, than cells from healthy controls (P < 0Á03 to P < 0Á04). Five patients with MS and no controls, displayed MBP-induced CD4 + T-cell proliferation. These high-responders exhibited enhanced production of IL-17, IFN-c, IL-5 and IL-4 upon challenge with MBP, as compared with the remaining patients and the healthy controls (P < 0Á002 to P < 0Á01). A strong correlation was found between the MBP-induced CD4 + T-cell proliferation and production of IL-17, IFN-c, IL-5 and IL-4 (P < 0Á0001 to P < 0Á01) within the patient group, and the production of IL-17 and IL-5 correlated with the number of active plaques on magnetic resonance images (P = 0Á04 and P = 0Á007). These data suggest that autoantigendriven CD4 + T-cell proliferation and release of IL-17 and IL-5 may be associated with disease activity. Larger studies are needed to confirm this.

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Section: Measurement Of Cd4mentioning

confidence: 99%

T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

et al. 2008

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“…In a GD model, Pichurin et al (12) showed that B cell-deficient mice were unable to elicit the normal T cell response to immunization with TSH-R. Conversely, the production of autoantibodies seems dependent on the help of CD4 þ T cells (53). In a human in vitro system, we have demonstrated (36) that depletion of peripheral blood mononuclear cells for B cells markedly reduced CD4 þ T cell responses to Tg in healthy individuals, and that formation of complement-activating immune complexes between Tg and Tg-reactive natural antibodies promoted the response of Tg-reactive CD4 þ T cells (36). Moreover, the presence of Tgabs from patients with HT further enhanced this T cell response (39).…”

Section: B/t Cell Interaction: the B Cell As An Antigenpresenting Cellmentioning

confidence: 65%

“…In addition to being precursor cells for the Ig (and autoantibody)-secreting plasma cells, B cells are also known as critical APCs in AITD (9,10,36,39) and other autoimmune diseases (5 -8), a role which may be partly dependent upon complement and autoantibodies as shown for Tgabs (36,39).…”

Section: Adverse Effects Of Rtx Treatmentmentioning

confidence: 99%

“…TPOabs and Tgabs can be detected in approximately 70% and 50% respectively of patients with GD (1). The thyroid autoantibodies are, however, not specific for thyroid autoimmunity (34) and, although being useful in clinical routine, a clear distinction between autoantibody positivity and negativity is of limited value in immunological terms since, for example, circulating Tgabs can be found in practically all individuals (35,36). These antibodies belong to the so-called natural autoantibodies that are encoded by immunoglobulin (Ig)-variable genes in germ-line configuration and exhibit low-affinity binding to wellconserved epitopes of a broad variety of foreign and self antigens (37,38).…”

Section: Introductionmentioning

confidence: 99%

“…They exhibit a less restricted idiotype pattern than disease-associated antibodies (35). We have shown that natural Tgabs are instrumental in mediating the uptake and presentation of Tg by B cells, a mechanism that might be involved in maintaining peripheral tolerance to Tg (36). The fraction of Tg-responsive B cells and CD4 þ T cells in a healthy individual can be raised considerably by increasing the Tgab concentration in the environment (39).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

Fassi¹,

Nielsen²,

Hasselbalch³

et al. 2006

eur j endocrinol

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We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after reviewing the efficacy and safety in other autoimmune diseases, we propose that treatment with the B celldepleting agent Rituximab may become a clinically relevant treatment option in selected cases of GD, particularly when complicated with thyroid-associated ophthalmopathy.European Journal of Endocrinology 154 623-632

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Autoantibodies in Autoimmune Thyroid Disease

Martinez

Prabhakar

2005

Autoantibodies and Autoimmunity

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Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4+ T cells in healthy individuals

Cited by 56 publications

References 41 publications

T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

Autoantibodies in Autoimmune Thyroid Disease

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