T cells from atopic individuals produce IgE‐inducing activity incompletely blocked by anti‐interleukin‐4 antibody

Zhang, Xiaohong; Polla, Barbara S.; Hauser, Conrad; Zubler, Rudolf H.

doi:10.1002/eji.1830220330

Cited by 27 publications

(16 citation statements)

References 29 publications

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“…Differential expression of other cytokines or membrane-associated molecules, important for IgB production, such as the ligand for CD40, might cause a lack of correlation of IL-4 with IgE production in the atopic group. We believe that the presence of another IgE-inducing cytokine in the atopic group would be the most likely explanation, for the following reasons: (i) the mean individual ratio of IgE lo IL-4 was higher in atopic donors (r = 0020) than in normal donors [r = 0 015, not shown); (ii) IgE-inducing activity in supernatants of T cells from atopic donors could not be inhibited completely by anti-IL-4 [43]; (iii) in our study IgE production by lymphocytes from an atopic donor with high IgE production and low IL-4 production was only slightly inhibited by anti-IL-4; (iv) in T cell clones, isolated from a patient with a hyper-IgE syndrome, IL-4 production was not correlated with help for IgE production [27]. These data all point to the possible involvement of another IgE-inducing cytokine.…”

Section: Discussionmentioning

confidence: 99%

IgE production in atopic patients is not related to IL-4 production

Kraan¹,

Aalberse²,

Aarden³

1994

Clinical and Experimental Immunology

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SUMMARYTo analy.se whether there is a general defect in T or B cell function in atopic individuals we have measured cytokine and IgE production by peripheral blood lymphocytes, isolated from 19 atopic donors (17 asthma/rhinitis and two dermatitis patients) in comparison with 19 non-atopic controls. After stimulation oflymphocytes with aiiti-CD2 and anti-CD28. we found no significant difference in IL-2, IL-4 and interferon-gamma (IEN--)) production. To examine the correlation between the production of IgE and IL-4, we stimulated lymphocytes with anti-CD2 and rIL-2. Under this condition both T eell iL-4 and B cell IgE production ean be measured. No significant diflerence was found for the amount of IgE and IL-4 produced between the two groups ( P > 005). The non-atopie donors showed a good correlation between IL-4 and IgE production (r = 0'70). Surprisingly, within the atopic group there was no correlation between IgE and IL-4 production at all (r = -0-04). The ratio of IgE to IL-4 was higher (although not signifieatitly) in the atopic group. Our data suggest that in atopic donors IgE production is less dependent on IL-4, and that other cytokines are involved.

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Section: Discussionmentioning

confidence: 99%

IgE production in atopic patients is not related to IL-4 production

Kraan¹,

Aalberse²,

Aarden³

1994

Clinical and Experimental Immunology

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“…The fact that activated human T cells produce the IgE switch factors IL-4 and IL-13 raises the possibility that both factors are involved in IgE responses in atopy [39,40]. crete IgE upon costimulation with anti-CD3 plus sCD40L.…”

Section: Pbmcfrom a Topic Individuals But Not From Nona Topic Controlmentioning

confidence: 99%

Role of IL-13 in CD4 T Cell-Dependent IgE Production in Atopy

Levy

Kristofic

Heusser

et al. 1997

Int Arch Allergy Immunol

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IgE isotype switching of human B cells requires physical interaction of T and B cells via surface molecules, and either IL-4 or IL-13 secreted by T cells. In this study we analyzed the role of IL-4 versus IL-13 in IgE production in atopy. We found that peripheral blood mononuclear cells (PBMC) from atopic individuals but not from nonatopic subjects secreted IgE without addition of IL-4 or IL-13, if T and B cells were simultaneously activated by anti-CD3 mAb and soluble CD40L, respectively. IgE production by atopic PBMC was dependent on endogenously secreted IL-4 and IL-13, since it could be blocked by a combination of anti-IL-4 plus anti-IL-13 antibodies. No differences in the B cell compartment of nonatopics and atopies were detectable, since PBMC from both donor populations secreted comparable amounts of IgE, if only the B cells were activated by soluble CD40L plus either exogenous IL-4 or IL-13. Further phenotypic analysis of T cells from atopies revealed that activated CD4+45RO– secreted IL-4 but no IL-13, whereas CD4+45RO+ memory T cells secreted low amounts of IL-4, but large amounts of IL-13. Accordingly, prolonged activation of naive CD4+45RO– T cells in vitro induced expression of CD45RO, and strongly favored secretion of IL-13 rather than IL-4. Addition of exogenous IL-4 during activation further increased both IL-4 and IL-13 production to a similar degree. However, the potential of CD4 T cells from atopies to deliver contact-dependent activation signals to B cells and to induce IgE production (in the absence of soluble CD40L) increased with prolonged activation, and coincided with IL-13 rather than IL-4 production. Under similar conditions, CD8 effector cells secreted IL-13 but no IL-4, did not express CD40L, and could not help Ig(E) production by B cells. These results suggest that, in atopy, persistently stimulated CD4+45RO+ memory/effector T cells provide contact-dependent activation signals to B cells, and that these cells may induce IgE switching largely via secretion of IL-13.

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“…Interestingly, IL–13–induced IgE synthesis has been found only in PBMC cultures from atopic, but not in those of healthy nonatopic individuals [15]. In addition, IL–4 inhibition was not found to be sufficient to suppress IgE in atopic diseases [15]. This may be due to the dominant IL–13 production by the CLA+ T cells which, therefore, may play an important role in the pathogenesis of chronic atopic inflammation.…”

Section: Both Cd4+ and Cd8+ Subsets Of Cla+ T Cells Induce Ige Producmentioning

confidence: 99%

“…As a consequence of their low cytokine synthesis, CLA+ T cells from nonatopic subjects induced only marginal IgE levels, whereas IgG4 was still induced by CLA– T cells [4]. Interestingly, IL–13–induced IgE synthesis has been found only in PBMC cultures from atopic, but not in those of healthy nonatopic individuals [15]. In addition, IL–4 inhibition was not found to be sufficient to suppress IgE in atopic diseases [15].…”

Section: Both Cd4+ and Cd8+ Subsets Of Cla+ T Cells Induce Ige Producmentioning

confidence: 99%

Regulation of Allergic Inflammation by Skin–Homing T Cells in Allergic Eczema

Akdiş¹,

Akdiş²,

Simon³

et al. 1999

Int Arch Allergy Immunol

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Background: In allergic inflammations of the skin, the pivotal role of CD45RO+ (memory/effector) T cells expressing the cutaneous lymphocyte–associated antigen (CLA) was demonstrated. In both atopic dermatitis (AD) and contact dermatitis (CD), T cells specific to skin–related allergens were confined to the CLA+ T cell population. Our research was aimed to further characterize these T cells in AD. Methods: CD4+ and CD8+ subsets of CLA+ CD45RO+ T cells were purified from peripheral blood of AD patients and healthy control individuals. We studied, in vivo activation patterns, cytokine profiles, immunoglobulin isotype regulation and the influence of these cells on eosinophil survival and apoptosis. Results: The CLA+ CD45RO+ T cells represent an in– vivo–activated memory/effector T cell subset as shown by surface expression of activation markers, spontaneous proliferation and a lower activation threshold via TCR/CD3 triggering. These cells contain and spontaneously release high amounts of preformed IL–5 and IL–13 but only very little IL–4 and IFN–γ in their cytoplasm, as demonstrated by intracellular cytokine staining immediately after purification. Moreover, CLA+ memory/ effector T cells induce IgE production in B cells and enhance eosinophil survival by inhibiting eosinophil apoptosis in AD. In comparison, the CLA– population represents a resting memory T cell fraction, induces rather IgG4 in B cells and does not show any effect on eosinophil survival and apoptosis. Conclusion: Our results indicate that in–vivo–activated both CD4+ and CD8+ memory/effector T cells with skin–homing property play a specific and decisive role in the pathogenesis and exacerbation of AD. In contrast, resting memory T cells of atopic individuals retain normal, nonallergic immune functions.

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T cells from atopic individuals produce IgE‐inducing activity incompletely blocked by anti‐interleukin‐4 antibody

Cited by 27 publications

References 29 publications

IgE production in atopic patients is not related to IL-4 production

IgE production in atopic patients is not related to IL-4 production

Role of IL-13 in CD4 T Cell-Dependent IgE Production in Atopy

Regulation of Allergic Inflammation by Skin–Homing T Cells in Allergic Eczema

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