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H Renz

Publications and source records attributed to H Renz.

At least 73 records · Page 4Linked to original sources
PubMed1999

Specific V beta T cell subsets are associated with cat and birch pollen allergy in humans.

Cognate interaction between TCRs and MHC class II molecules plays an important role in initiating the allergen-specific immune response. Therefore, we analyzed the TCR distribution of human PBLs of 56 atopic and nonatopic (NA) individuals, including 4 monozygotic twin pairs, from two extended and four nuclear families. The expression of 23 V beta and 3 V alpha elements was analyzed. The blood samples of symptomatic birch pollen-sensitized individuals that were taken < or = 6 wk after the birch pollen season (n = 8) showed a significantly higher frequency of V beta 16.1+ and V beta 20.1+ T cells compared with the blood samples of birch pollen-sensitized individuals that were obtained out of allergen season (n = 10) or from NA individuals (p < 0.0005 and p < 0.0001, respectively). Allergen-specific lymphocyte proliferation was detected in the allergic individuals, and the distribution of V beta 16.1+ and V beta 20.1+ T cells returned to normal levels after the pollen season. The frequency of these V beta-expressing T cells correlated with the levels of allergen-specific IgE Abs. In addition, cat-sensitized individuals (n = 8) showed a significantly higher frequency of V beta 17.1-expressing T cells than did NA individuals (p < 0.005). Our results indicate restricted TCR-V beta gene usage in cat and birch pollen allergies; we suggest that both genetic and environmental factors contribute to TCR-V beta gene expression and to the development of a specific T cell response.

Adolescent↗
PubMed1999

Airway exposure to bacterial superantigen (SEB) induces lymphocyte-dependent airway inflammation associated with increased airway responsiveness--a model for non-allergic asthma.

Although immunological consequences of systemic superantigen administration have been extensively studied, the effects of local mucosal exposure to superantigens are not well defined. The purpose of this study was to delineate the type of immune response triggered by superantigen exposure to the airway mucosa in mice. In dose-response experiments we determined a low dose of staphylococcal enterotoxin B (SEB) that triggered an inflammatory response characterized by mucosal and airway recruitment of lymphocytes, eosinophils and neutrophils together with elevated levels of IL-4, but not IFN-gamma, in bronchoalveolar lavage (BAL) fluids. TCR Vbeta analysis revealed that superantigen-responsive and -non-responsive T cells were equally recruited into the airways. SEB markedly enhanced the frequency of TNF-alpha-positive BAL macrophages as well as the amount of TNF-alpha in BAL fluids. These responses were associated with the development of increased airway responsiveness (AR) in SEB-treated mice. This effect occurred in an antibody-independent fashion. Furthermore, this type of response was observed in IgE-high responder BALB/c as well as in IgE-low/intermediate responder C57BL/6 mice. The development of increased AR was CD4+ T cell dependent as shown by transfer experiments into BALB/c nu/nu mice. These results suggest that the local immune response following mucosal superantigen administration triggers a unique inflammatory response in the airways resembling many features of "intrinsic asthma".

Administration, Intranasal↗
PubMed1999

Impact of V beta 8+/+ T cells on the development of increased airway reactivity and IgE production in SJL mice.

SJL mice have been extensively characterized as "low-responder" animals in terms of IgE-dependent immediate-type hypersensitivity responses. Since these mice are genetically deficient in certain TCR Vbeta gene segments, we asked whether this might be the reason for the "low-responder" status. Specifically in H-2d mice the TCR-Vbeta8.2 gene element has been shown to play an important role in Th2 immune responses to ovalbumin (OVA). Utilizing a TCR Vbeta8. 2-transgenic SJL (SJL Vbeta8+/+) mouse, we examined whether the H-2s -bearing "low-responder" mouse could be converted into a "high-responder" animal. Remarkably, non-sensitized SJL Vbeta8+/+ mice demonstrated strongly elevated levels of total IgE antibody. Mitogen-stimulated T cells from these mice released high amounts of IL-4 as compared to SJL wild-type (wt) mice. In addition, sensitization to OVA via the airways resulted in the development of increased airway responsiveness in SJL Vbeta8+/+ mice, but not in SJL wt animals. The results indicate that the capacity to produce IgE and IL-4 and to develop increased airway responsiveness can be restored in SJL wt mice by introducing the Vbeta8.2 gene segment into the TCR repertoire.

Allergens↗
PubMed1999

Soluble interleukin-4 receptor (sIL-4R) in allergic diseases.

The mediator interleukin-4 (IL-4) plays an important role in the development of allergic inflammatory responses. IL-4 controls the production of IgE, expands IL-4 producing T cell subsets and stabilises effector cells functions. Based on this concept, it was aimed to neutralize secreted IL-4 molecules using recombinant soluble IL-4 receptors. The molecular characterization of soluble IL-4 receptors allowed the design of a recombinant drug initially evaluated in cell culture, then in animal models, followed by investigations of T cell functions from allergic patients in vitro. Based on these data, phase I/II studies have been initiated to take this approach from bench to bedside. Initial data reveal that this approach is safe and without drug-related toxicity. Stabilization of lung functions in moderate asthma patients has been reported. These results have proven the concept for a central role of IL-4 in the immunopathogenesis of allergic diseases. The immediate future will reveal whether neutralization of IL-4 with suitable drugs will provide an additional tool in the management of allergic patients.

Animals↗
PubMed1999

Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions.

Brain-derived neurotrophic factor (BDNF) plays a crucial role for the survival of visceral sensory neurons during development. However, the physiological sources and the function of BDNF in the adult viscera are poorly described. We have investigated the cellular sources and the potential role of BDNF in adult murine viscera. We found markedly different amounts of BDNF protein in different organs. Surprisingly, BDNF levels in the urinary bladder, lung, and colon were higher than those found in the brain or skin. In situ hybridization experiments revealed that BDNF mRNA was made by visceral epithelial cells, several types of smooth muscle, and neurons of the myenteric plexus. Epithelia that expressed BDNF lacked both the high- and low-affinity receptors for BDNF, trkB and p75(NTR). In contrast, both receptors were present on neurons of the peripheral nervous system. Studies with BDNF-/-mice demonstrated that epithelial and smooth muscle cells developed normally in the absence of BDNF. These data provide evidence that visceral epithelia are a major source, but not a target, of BDNF in the adult viscera. The abundance of BDNF protein in certain internal organs suggests that this neurotrophin may regulate the function of adult visceral sensory and motor neurons.

Animals↗
PubMed1999

Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type I allergy.

BACKGROUND: Mucosal (nasal or oral) administration of soluble protein antigens induces a state of antigen-specific immunologic hyporesponsiveness. Several studies have shown that induction of mucosal tolerance can prevent the onset or reduce the severity of certain TH1 -mediated experimental autoimmune diseases. Only a few studies describe similar results for type I allergies, which are caused by excessive TH2 cell activities. OBJECTIVE: We sought to investigate whether mucosal tolerance induction would also be efficient in preventing an allergic type I immune response. METHODS: A murine model of inhalative type I allergy, leading to sensitization to birch pollen and its major allergen Bet v 1 in BALB/c mice, was used. Recombinant Bet v 1 was nasally or orally applied in low doses before sensitization. At the time of death, immediate-type skin tests were performed. Blood was taken, and serum was used for measurement of allergen-specific antibodies. Spleen cell cultures were performed to determine cytokine production (IL-4, IL-5, IL-10, and IFN-gamma), as well as levels of TGF-beta mRNA. RESULTS: Both nasal and oral administration of minimal doses of recombinant Bet v 1 before aerosol sensitization with birch pollen suppressed the allergen-specific antibody production of all isotypes. Consequently, the in vivo type I skin test responses to the allergen were negative in the tolerized, in contrast to the sensitized, group. Moreover, allergen-specific lymphoproliferative responses and cytokine production in vitro (ie, IFN-gamma, IL-4, IL-5, and IL-10) were markedly reduced. In contrast, expression of TGF-beta mRNA was markedly increased in spleen cells from nasally tolerized animals, indicating regulatory mechanisms for tolerance induction. CONCLUSION: We conclude from the present study that nasal, as well as oral, administration of recombinant allergen is an effective way to prevent allergen-specific T- and B-cell responses in a TH2 model.

Administration, Intranasal↗
PubMed1999

Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis.

BACKGROUND: The skin of patients with atopic dermatitis exhibits a striking susceptibility to colonization and infection with Staphylococcus aureus. In this context it has been previously shown that S aureus-derived superantigens could function as classic allergens, inducing production of functionally relevant specific IgE antibodies. OBJECTIVE: The aim of this study was to determine the prevalence and the role of circulating staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)-specific IgE antibodies in children with atopic dermatitis. METHODS: In a cross-sectional study of 58 children with atopic dermatitis, the presence of IgE antibodies to SEA and SEB was correlated with the severity of the disease and the total and other unrelated allergen-specific IgE titers and density of colonization with S aureus strains on atopic skin and episodes of superficial S aureus skin infections. RESULTS: Twenty of 58 children (34%) were sensitized to superantigens (45% to SEB, 10% to SEA, 45% to SEA and SEB). In this group, severity of atopic dermatitis and levels of specific IgE to food and air allergens were significantly higher. The degree of disease severity correlated to a higher extent with the presence of SEA/SEB-specific antibodies than with total serum IgE levels. Density of colonization with superantigen-secreting S aureus strains was higher in the superantigen IgE-positive group. Sixty-three percent of these children experienced repeated episodes of superficialS aureus skin infections. CONCLUSIONS: Sensitization to S aureus-derived superantigens may be involved in disease exacerbation. The presence of SEA/SEB-specific antibodies had additional explanatory value for disease severity and therefore may be helpful in the characterization of children with severe atopic dermatitis.

Adolescent↗
PubMed1999

Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification.

Living conditions in eastern Germany have changed rapidly since unification in 1990 and little is known about how these changes affect the prevalence of atopic diseases. This study describes methods and prevalences of a large epidemiological project investigating determinants of childhood asthma and allergies in eastern (Dresden and Leipzig) and western (Munich) Germany in 1995/1996. Community based random samples of 9-11 yr old children in Dresden (n=3,017) and Munich (n=2,612), and of 5-7 yr old children in Dresden (n=3,300), Leipzig (n=3,167) and Munich (n=2,165) were studied by parental questionnaires, bronchial challenges with hypertonic saline, skin examination, skin-prick tests, and measurements of specific and total serum immunoglobulin (Ig)E using Phase II modules of the International Study of Asthma and Allergies in Childhood (ISAAC). In 9-11 yr old children, the prevalence of physician diagnosed asthma (7.9% versus 10.3%; p<0.01) and bronchial hyperresponsiveness (15.7% versus 19.9%; p<0.05) was lower in Dresden than in Munich. No difference between Munich and Dresden was observed in the prevalence of diagnosed hay fever, skin test reactivity to > or = 1 allergen, and increased levels (>0.35 kU x L(-1)) of specific IgE against inhalant and food allergens. Symptoms and visible signs of atopic eczema tended to be more prevalent in Dresden. Similar East-West differences between the three study areas were seen in the younger age group. These findings are in line with recently observed increases in the prevalence of hay fever and atopic sensitization, but not of asthma and bronchial hyperresponsiveness, among 9-11 yr old children in Leipzig.

Air Pollution↗
PubMed1999

Modified T-cell activation pattern during specific immunotherapy (SIT) in cat-allergic patients.

OBJECTIVE: The aim of the study was to analyse early effects of specific immunotherapy (SIT) on immune functions in cat-allergic patients. METHODS: Immunological responses of peripheral blood mononuclear cells from eight cat-allergic patients were analysed before and after SIT in comparison with 11 nonallergic controls. Cells were stimulated in vitro with either bacterial superantigen, mitogen, or cat allergen. Production of IL-12 and TH1/TH2 cytokines was analysed by ELISA and lymphocyte subset distribution was assessed by flow-cytometry. RESULTS: We found a significantly reduced secretion of IL-12 (P < 0.05) from cells of allergic individuals compared with the controls. This finding was associated with significantly lower IFN-gamma production after stimulation with allergen (P < 0.05) that did not increase during SIT. However, no significant differences were seen after stimulation with mitogen indicating an allergen specific IFN-gamma secretion response in allergic individuals. Prior to SIT IL-5 production was significantly higher in cells of allergic donors stimulated with allergen < 0.005 or mitogen (< 0.05). After reaching the maintenance dose for SIT, allergen-induced IL-5 production returned to normal levels, whereas it remained elevated after stimulation with mitogen. These changes were associated with a reduced frequency of CD45 RO T cells following SIT. CONCLUSION: These results suggest that SIT exerts early effects on allergen-specific T-cell responses with selective inhibition of the up-regulated TH2 immune response.

Allergens↗
PubMed1999

A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control.

Neurotrophins exert many biological effects not directly targeted at neurons, including modulation of keratinocyte proliferation and apoptosis in vitro. Here we exploit the cyclic growth and regression activity of the murine hair follicle to explore potential nonneuronal functions of neurotrophins in the skin, and analyze the follicular expression and hair growth-modulatory function of BDNF, NT-4, and their high-affinity receptor, TrkB. The cutaneous expression of BDNF and NT-4 mRNA was strikingly hair cycle dependent and peaked during the spontaneous, apoptosis-driven hair follicle regression (catagen). During catagen, BDNF mRNA and immunoreactivity, as well as NT-4-immunoreactivity, were expressed in the regressing hair follicle compartments, whereas TrkB mRNA and immunoreactivity were seen in dermal papilla fibroblasts, epithelial strand, and hair germ. BDNF or NT-4 knockout mice showed significant catagen retardation, whereas BDNF-overexpressing mice displayed acceleration of catagen and significant shortening of hair length. Finally, BDNF and NT-4 accelerated catagen development in murine skin organ culture. Together, our data suggest that BDNF and NT-4 play a previously unrecognized role in skin physiology as agents of hair growth control. Thus, TrkB agonists and antagonists deserve exploration as novel hair growth-modulatory drugs for the management of common hair growth disorders.

Animals↗
PubMed1999

T cell receptor vbeta repertoire in bronchoalveolar lavage in Wegener's granulomatosis and sarcoidosis.

BACKGROUND: Lymphocytic alveolitis is a common feature of Wegener's granulomatosis (WG) and sarcoidosis. In pulmonary sarcoidosis analysis of the T cell receptor (TCR) configuration disclosed a biased TCR repertoire in cells obtained by bronchoalveolar lavage (BAL), suggesting that the pulmonary T cell population contains an oligoclonal, probably antigenically selected component. We examined whether this is also a feature of WG. METHODS: The distribution of 16 TCR Vbeta phenotypes on BAL cells was compared with the distribution on autologous blood cells in 8 WG patients with lymphocytic alveolitis. A control group was composed of 5 patients with active pulmonary sarcoidosis. The two groups were comparable with respect to the lymphocyte count in BAL and the distribution of the CD4+ and CD8+ T cell subsets in BAL and the blood. Overutilization of individual Vbeta phenotypes on BAL cells was considered to be significant when the percentage of positive cells in BAL doubled than in the blood and the frequency in BAL was at least 10% of total BAL T cells. RESULTS: All 5 sarcoidosis patients showed substantial overutilization of individual Vbeta families in BAL as compared with the blood. By contrast, only 2 of the 8 WG patients showed overutilization of individual Vbeta phenotypes in BAL. CONCLUSIONS: These findings do not suggest that the T cell population in BAL of WG patients contains a prominent oligoclonal component. While BAL is a convenient approach to obtain T cells from a site of active disease, BAL cells do not appear to be good material for the isolation of clonally selected T cells in WG.

Adult↗
PubMed1999

Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation.

The aim of this study was to investigate production and cellular sources of brain-derived neurotrophic factor (BDNF) production in allergic asthma. For this purpose a mouse model of chronic and severe ovalbumin (OVA)-induced airway inflammation was developed. Allergen-exposed mice developed elevated immunoglobulin E titers; airway inflammation with influx of lymphocytes, monocytes, and eosinophils; and airway hyperresponsiveness. In addition to an influx of inflammatory cells, interleukin (IL)-4 and IL-5 production were enhanced, macrophages showed morphologic signs of activation, and airway epithelium was thickened and displayed a goblet-cell hyperplasia with a marked mucus production. BDNF was detected using in situ hybridization and enzyme-linked immunosorbent assay. Constitutive expression of BDNF messenger RNA (mRNA) was observed in the respiratory epithelium of sensitized and nonsensitized mouse lungs. In addition, BDNF mRNA was detected in airway inflammatory infiltrations and bronchoalveolar lavage fluid (BALF) cells of OVA-sensitized and aerosol-challenged mice. Highest BDNF protein levels were detected in BALF after long-term allergen aerosol exposure. Analysis of BDNF production by isolated lymphocyte subsets revealed T but not B cells as a cellular source of BDNF. In addition, activated alveolar macrophages were identified as BDNF-positive cells. These data indicate that in allergic airway inflammation BDNF production is upregulated and immune cells serve as a source of BDNF.

Allergens↗
PubMed1999

Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 act as "epitheliotrophins" in murine skin.

Nerve growth factor (NGF) is produced by keratinocytes and modulates their proliferation and apoptosis. However, it is as yet unknown whether other members of the NGF family of neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), also modulate keratinocyte proliferation in situ. We determined by ELISA and reverse transcriptase-PCR that BDNF, NT-3, and NT-4 are expressed in C57BL/6 mouse skin. By immunofluorescence, the subcutaneous panniculus carnosus muscle and arrector pili muscle showed strong NT-3 immunoreactivity, whereas BDNF-IR was found only in skin nerve bundles. NT-4 immunoreactivity was noted in single epidermal keratinocytes. The high affinity receptor for both BDNF and NT-4, TrkB, was detected in basal and suprabasal epidermal keratinocytes, whereas the high affinity NT-3 receptor, TrkC, was observed in skin nerve bundles. Compared with the corresponding age-matched wild-type mice, BDNF or NT-3-overexpressing transgenic mice showed a significantly increased epidermal thickness and enhanced number of Ki-67-positive (ie, proliferating) epidermal keratinocytes in vivo, whereas the number of these cells was substantially reduced in BDNF knockout mice. In skin organ culture of C57BL/6 mice, BDNF, NT-3, and NT-4 all significantly increased 5-bromo-2'-deoxyuridine incorporation into epidermal keratinocytes. Co-administration of NGF neutralizing antibody failed to abrogate the stimulatory effect of NT-3 on keratinocyte proliferation in skin organ culture. This demonstrates that normal murine epidermal keratinocytes in situ are direct or indirect target cells for these neurotrophins. Therefore, BDNF, NT-3, and NT-4 can also act as "epitheliotrophins" and may thus be intimately involved in the control of epidermal homeostasis.

Animals↗
PubMed1998

Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma.

The role of nerve growth factor (NGF), a potent mediator acting in the development and differentiation of both neuronal and immune cells, was examined in a mouse model of allergic asthma. NGF-positive cells were detected in the inflammatory infiltrate of the lung and enhanced levels of NGF were detected in serum and broncho-alveolar lavage fluids. Mononuclear cells in inflamed airway mucosa as well as broncho-alveolar macrophages were identified as one source of NGF production. Splenic mononuclear cells from allergen-sensitized mice produced NGF in response to allergen. They responded to exogenously added NGF with a dose-dependent increase in IL-4 and IL-5 production and augmented IgE and IgG1 synthesis. In contrast, IFN-gamma and IgG2alpha levels remained unaffected. The effects were NGF specific, since they could be blocked by an anti-NGF-antibody. Nasal application of anti-NGF to allergen-sensitized mice significantly reduced IL-4 and prevented development of airway hyperreactivity. These results show that allergic airway inflammation is accompanied by enhanced local NGF production that acts as an amplifier for Th2 effector functions and plays an important role in the development of airway hyperreactivity. Therefore it is suggested that NGF may serve as a link between the immune and nerve system.

Allergens↗
PubMed1998

IL-15-IgG2b fusion protein accelerates and enhances a Th2 but not a Th1 immune response in vivo, while IL-2-IgG2b fusion protein inhibits both.

We have explored how IL-15 influences Th1 or Th2 type immune response in vivo. Intraperitoneal application of an IL-15-IgG2b fusion protein (FP) to mice did neither significantly affect the footpad swelling nor the production of hemagglutinizing antibodies in a delayed type hypersensitivity reaction to sheep red blood cells. In contrast, in an established murine Th2 model of sensitization to ovalbumin (OVA), IL-15-IgG2b FP plus OVA sensitization resulted in massively accelerated and enhanced allergen-specific IgE and IgG1 antibody production. In vitro, stimulation of spleen cells from OVA-sensitized mice with OVA+IL-15 or OVA+IL-15-IgG2b resulted in a significantly enhanced IgE production. IL-4 secretion was significantly induced by IL-15 but not by IL-15-IgG2b. An IL-2-IgG2b FP with the same Fc tail as the IL-15-IgG2b FP was used as control in both models. In striking contrast to the IL-15-IgG2b FP, IL-2-IgG2b significantly inhibited the Th2 type antibody production in vivo. The current study suggests that IL-15-IgG2b may be employed as a potent accelerator and enhancer of Th2 type immune responses in vivo, while IL-2-IgG2b can suppress the latter.

Allergens↗
PubMed1998

A scanning electron-microscopic study of developing human deciduous enamel on the dependence of the outline of surface pits on the angle of observation.

On the developing enamel surfaces of fetal human deciduous teeth, many of the surface pits were arcade-shaped with the arcade preferentially pointing in a cervical direction. The configuration of the interprism ridges between the pits contributed to this appearance. Surface cracks allowed verification of an incisal inclination of the subsurface prisms. This apparent paradox was solved when the specimens were tilted so that the pits were viewed in the directions of the prisms, giving the pits a compressed arcade-shape with the arcades pointing incisally. It is recommended that care should be exercised and due attention paid to the angle of observation when determining the orientation of pit arcades. Pit entry direction seems to be a more reliable feature for inferring the direction of tangential ameloblast movement.

Ameloblasts↗