T Regulatory-1 Cells Induce IgG4 Production by B Cells: Role of IL-10

Satoguina, Judith; Weyand, Esther; Larbi, John Asiedu; Hoerauf, Achim

doi:10.4049/jimmunol.174.8.4718

Cited by 160 publications

(132 citation statements)

References 58 publications

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“…Confirming earlier reports, our present analysis revealed the existence of a subgroup of donors with skewed IgG subclass distribution with low to absent specific IgG1 and predominant IgG4 expression ( Fig. 1) (37)(38)(39), a clinical finding associated with chronic Ag exposure, elevated IL-10 levels, and parasitic infections (40,41). Well in line with this observation Walker et al (42) described predominance of IgG2 in PBMC stimulated with SAC.…”

Section: Analysis Of S Aureus-specific Serum Igg Reveals Predominancsupporting

confidence: 79%

Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus

Parčina

Miranda-García

Durlanik

et al. 2013

The Journal of Immunology

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Induction of polyclonal B cell activation is a phenomenon observed in many types of infection, but its immunological relevance is unclear. In this study we show that staphylococcal protein A induces T cell–independent human B cell proliferation by enabling uptake of TLR-stimulating nucleic acids via the VH3+ BCR. We further demonstrate that Staphylococcus aureus strains with high surface protein A expression concomitantly trigger activation of human plasmacytoid dendritic cells (pDC). Sensitivity to chloroquine, cathepsin B inhibition, and a G-rich inhibitory oligodeoxynucleotide supports the involvement of TLR9 in this context. We then identify pDC as essential cellular mediators of B cell proliferation and Ig production in response to surface protein A–bearing S. aureus. The in vivo relevancy of these findings is confirmed in a human PBMC Nod/scidPrkdc/γc−/− mouse model. Finally, we demonstrate that co-operation of pDC and B cells enhances B cell–derived IL-10 production, a cytokine associated with immunosuppression and induction of IgG4, an isotype frequently dominating the IgG response to S. aureus. IL-10 release is partially dependent on TLR2-active lipoproteins, a hallmark of the Staphylococcus species. Collectively, our data suggest that S. aureus exploits pDC and TLR to establish B cell–mediated immune tolerance.

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Section: Analysis Of S Aureus-specific Serum Igg Reveals Predominancsupporting

confidence: 79%

Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus

Parčina

Miranda-García

Durlanik

et al. 2013

The Journal of Immunology

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“…Also, human studies strongly support the notion that IL-10 is a key mediator of nematode-induced immune suppression (46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 55%

Pathogenic Nematodes Suppress Humoral Responses to Third-Party Antigens In Vivo by IL-10–Mediated Interference with Th Cell Function

Hartmann

Haben

Fleischer

et al. 2011

The Journal of Immunology

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One third of the human population is infected with helminth parasites. To promote their longevity and to limit pathology, helminths have developed several strategies to suppress the immune response of their host. As this immune suppression also acts on unrelated third-party Ags, a preexisting helminth infection may interfere with vaccination efficacy. In this study, we show that natural infection with Litomosoides sigmodontis suppressed the humoral response to thymus-dependent but not to thymus-independent model Ags in C57BL/6 mice. Thereby, we provide evidence that reduced humoral responses were mediated by interference with Th cell function rather than by direct suppression of B cells in L. sigmodontis-infected mice. We directly demonstrate suppression of Ag-specific proliferation in OVA-specific Th cells after adoptive transfer into L. sigmodontis-infected mice that led to equally reduced production of OVA-specific IgG. Transferred Th cells displayed increased frequencies of Foxp3+ after in vivo stimulation within infected but not within naive mice. Helminth-mediated suppression was induced by established L. sigmodontis infections but was completely independent of the individual worm burden. Using DEREG mice, we rule out a central role for host-derived regulatory T cells in the suppression of transferred Th cell proliferation. In contrast, we show that L. sigmodontis-induced, host-derived IL-10 mediated Foxp3 induction in transferred Th cells and significantly contributed to the observed Th cell hypoproliferation within infected mice.

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“…In addition, in IgE-mediated allergic disease, however, there is renewed interest for determining specific IgG: IgG4, formed in the course of allergen-specific immunotherapy, not only shows blocking activity by inhibiting IgE-mediated facilitated antigen presentation (7), increasing evidence points to the conclusion that allergenspecific IgG4 responses are the result of the activities of regulatory T cells, being associated with the induction of immunological tolerance upon prolonged exposition to antigen (8). One of the main characteristics of Treg cells is the secretion of interleukin (IL)-10, which leads to the formation of an antigen-specific, noncomplementactivating, IgG4 response (9,10).…”

Section: Igg Testing In Allergymentioning

confidence: 99%

Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report*

Stapel¹,

Asero²,

Ballmer‐Weber³

et al. 2008

Allergy

220

132

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KEYWORDS food allergy • food intolerance • IgG • IgG4 • in vitro tests ABSTRACTSerological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints. ARTICLE TEXTAn adverse food reaction is a general term describing clinically abnormal responses to an ingested food that might occur secondary to nonallergic food hypersensitivity (food intolerance) or allergic food hypersensitivity (food allergy).Food allergy is an immunologic reaction that involves in particular the immunoglobulin E (IgE) mechanism, of which anaphylaxis is the classic example.Food intolerance, however, is a general term, describing an abnormal physiologic response to an ingested food or food additive. Diagnosis of food allergy aims to establish a reliable link between the clinical history of an adverse reaction to food as reported by the patient and the immunological basis of this reaction. In food allergy, an accurate diagnosis is extremely important, in particular to prevent patients from unnecessary and even potentially health threatening diets.Measurement of food-specific IgE antibodies by in vitro assays or skin testing are the routine procedures to diagnose food allergy. These diagnostic tests, however, indicate the presence of food-specific IgE antibodies, but they do not establish the diagnosis of food allergy. The final proof of the clinical relevance of the reported

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T Regulatory-1 Cells Induce IgG4 Production by B Cells: Role of IL-10

Cited by 160 publications

References 58 publications

Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus

Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10–Producing B Cells in Response to Staphylococcus aureus

Pathogenic Nematodes Suppress Humoral Responses to Third-Party Antigens In Vivo by IL-10–Mediated Interference with Th Cell Function

Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report*

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