Th1-Zellen, Th2-Zellen und atopische Dermatitis
ABSTRACT Die zugunsten der Th2-Zellen verschobene Th1/Zh2-Balance ist ein wesentliches Charakteristikum der atopischen Dermatitis (AD).
Die Reaktion auf hochmolekulare Umweltallergene (z.B. Pollen, Hausstaubmilben), Produktion des IgE und Aktivierung von eosinophilen
Granulozyten sind Folge der Th2-Dominanz. Das Th2-Zytokin Interleukin-4 (IL-4) ist für die IgE-Synthese erforderlich. Außerdem
inhibiert IL-4 die Generierung von Th1-Zellen. Reziproke Eigenschaften besitzt das Markerzytokin der Th1-Zellen, das Interferon
γ (IFNγ). Es hemmt die IgE-Synthese und die Th2-Expansion, fördert aber das Th1-Zellwachstum. Während die Mechanismen IgE-mediierter
Soforttyp- Reaktionen schon länger bekannt sind, wurde die Bedeutung des IgE für die AD erst durch die Entdeckung von IgE-Rezeptoren
auf der Langerhans-Zelloberfläche wahrscheinlich gemacht. Vermutlich ist das Langerhans-Zell-gebundene IgE für die Präsentation
hochmolekularer Aeroallergene erforderlich. Th-Analysen zu unterschiedlichen Zeiten nach Allergenexposition zeigten, daß Th2-Zellen
offenbar in der Initialphase inflammatorischer Reaktionen eine wichtige Rolle spielen, während in späteren Phasen auch Th1-Zellen
in größerem Umfang nachgewiesen werden können.
The immunological hallmark of atopic dermatitis (AD) is a Th1/Th2 dysbalance. The reaction to high molecular weight environmental
allergens (e.g. pollen, house dust mites),production of IgE and activation of eosinophil granulocytes result from Th2 dominance.
The Th2-cytokine interleukin-4 (IL-4) is necessary for IgE synthesis. Additionally, IL-4 inhibits the generation of Th1-cells.
The marker cytokine of Th1-cells, interferon γ (IFNγ), exhibits reciprocal effects. It inhibits IgE synthesis and Th2 expansion,
but supports Th1-cell growth. Beside the well known mechanisms of IgE-mediated immediate type reactions, the relevance of
IgE for the pathogenesis of AD seems to be likely since the discovery of IgE-receptors upon Langerhans cell surfaces. Langerhans
cell-bound IgE may be possibly neccessary for the presentation of high molecular weight aero-allergens. Analyses of Th subsets
at different intervals after allergen challenge showed, that Th2-cells play an important role in the initial phase of inflammatory
reactions whereas in later stages Th1-cells can be detected in greater numbes.
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ABSTRACT: Cell-mediated hypersensitivity (CMH) to house dust mite antigens, as determined by increased DNA synthesis after coculture of mononuclear cells with Dermatophagoides farinae extract, was demonstrated in 11 of 16 children with atopic dermatitis (AD) as compared with two of 14 control subjects. Patient and control responses peaked at the same antigen dose (12.4 micrograms of mite protein per 10(5) cells). Patient responses were significantly greater at all mite protein concentrations. The increased DNA synthesis of stimulated cells was demonstrated to be a T-cell response in the one patient in whom T-cell-enriched cultures were studied. There was no relationship between CMH and lgE-mediated hypersensitivity to D farinae in the patient group. It is suggested that AD is associated with CMH reactions to allergens and that antigen competition may be involved in the reduced CMH responses to mitogens and antigens noted by other investigators.Archives of Dermatology 02/1982; 118(1):26-9. · 4.79 Impact Factor
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ABSTRACT: A bias to either cell-mediated or antibody-mediated effector mechanisms is induced in an immune response against a pathogen, if activated T helper cells (Th) predominantly express Th1 [interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-beta] or Th2 (IL-4, IL-5, IL-6 and IL-10) cytokines. Here we provide evidence that, due to the capability to secrete IL-1, macrophages, but not B cells, as antigen-presenting cells (APC) induce production of IFN-gamma in resting Th cells. Normal murine splenic Th cells were activated in vitro with the superantigen Staphylococcus aureus enterotoxin B (SEB) presented by macrophages as compared to other APC from murine spleen. As determined by immunofluorescence, Th cells producing IL-2 but almost none producing IL-4 and IL-5 are generated, irrespective of the type of APC. Generation of IFN-gamma-producing Th cells is largely dependent on presentation of SEB by macrophages. The requirement for macrophages, however, is overcome if IL-1 is provided. Expression of IFN-gamma by Th cells is not induced, if production of IL-1 by macrophages is inhibited by IL-10. Our results suggest a functional dichotomy of APC: normal resting Th cells differentiate into IL-2 and IFN-gamma secreting cells (Th1 cells) if antigen is presented by macrophages, whereas presentation by B cells generates Th cells secreting IL-2, which might differentiate into Th2 cells upon re-stimulation.European Journal of Immunology 02/1993; 23(1):191-9. · 4.97 Impact Factor
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ABSTRACT: In atopic dermatitis (AD) hypersensitivity reactions to allergens are commonly observed and are assumed to make a major contribution in the pathomechanism of the disease. It may be expected that allergen-reactive Th cells play a central role in these reactions. In the present study the occurrence and function of allergen-specific T lymphocytes in dermal inflammatory lesions were studied. To this aim panels of randomly cloned CD4+ T cells from lesional skin biopsies of two housedust mite Dermatophagoides pteronyssinus (Dp)-allergic AD patients were screened for reactivity with Dp allergens. The results were compared with similar tests for Dp reactivity of T-lymphocyte clones (TLC) from the peripheral blood of these patients. In the panels of TLC generated from lesional skin (S-TLC), a considerable number of TLC appeared to be Dp-specific, 47% (n = 17) and 10% (n = 29), respectively. In the panels from the peripheral blood, the percentages of Dp-specific TLC were only 0% (n = 22) and 3% (n = 34), suggesting accumulation or expansion of these T cells in lesional skin. The function of these TLC was studied by assaying the secretion of IL-4 and IFN-gamma, which have been shown to be produced in aberrant ratios by Dp-specific TLC from the peripheral blood of AD patients (Wierenga et al: J Immunol 144:4651, 1990). All Dp-specific S-TLC produced IL-4 in combination with no or low levels of IFN-gamma, whereas many of the non-Dp-specific S-TLC and blood-derived TLC (B-TLC) were observed to produce high levels of IFN-gamma without significant amounts of IL-4. A functional consequence of these cytokine profiles was demonstrated by the finding that TLC producing substantial amounts of IL-4 enhanced expression of the low-affinity Fc receptor for IgE (CD23) on antigen-presenting cells to a greater extent than did IFN-gamma-producing TLC.Journal of Investigative Dermatology 10/1991; 97(3):389-94. · 6.19 Impact Factor