Cutaneous Hypersensitivity Reactions Research Articles

Priming of allergic immune responses by repeated ozone exposure in mice.

The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity (ICHS) reactions and antibody titers were assessed in parallel to cytokine levels of bronchoalveolar lavage fluids. In BALB/c mice, ozone triggered a T-helper (Th)2-like response indicated by dose-dependent increases in total serum immunoglobulin (Ig) E (from 133 to 821 ng/ml), interleukin (IL)-4 (from 60 to 208 pg/ml), and IL-5 levels (from 43 to 356 pg/ml), and by the recruitment of eosinophils and lymphocytes into the airways. Ozone exposure (500 microg/m(3)) in parallel to OVA-aerosol exposure increased anti-OVA IgG(1) antibody titers by 80%, leukotrienes (C(4)/D(4)/E(4)) by 60%, and airway responsiveness (11.3 versus 7.2 mg/ml methacholine), and doubled the frequency of positive ICHS reactions. In C57BL/6 mice, only the combination of OVA and ozone exposure induced positive ICHS reactions, doubled anti-OVA IgG(1), and suppressed anti-OVA IgG(2a) (-64%) antibody titers. Ozone, therefore, shifted the immune responses to OVA toward a Th2-like pattern in both "IgE-high responder" (BALB/c) and "IgE-low responder" (C57BL/6) mice.

Increased resistance to mycobacterial infection in the absence of interleukin-10.

Interleukin-10 (IL-10) down-regulates T helper type 1 cell and macrophage functions. As IL-10 is induced along with tumour necrosis factor (TNF) and IL-12 in mycobacterial infection, we asked whether endogenous IL-10 plays a role in the antimycobacterial response. We demonstrate here that IL-10-deficient mice eliminate Mycobacterium bovis Calmette-Guérin bacillus faster than wild-type mice. Granulomas are significantly larger, containing more CD-11b- and CD11c-positive antigen-presenting cells and T cells, and the expression of major histocompatibility complex class II and intracellular adhesion molecule-1 is increased. Macrophages in granulomas of IL-10-deficient mice express high levels of TNF, acid phosphatase and inducible nitric oxide synthase (iNOS). Finally, an increased cutaneous delayed-type hypersensitivity reaction to mycobacterial proteins is further evidence of an augmented cell-mediated immune response. In conclusion, the cell-mediated immunity is enhanced in the absence of IL-10, resulting in a robust granuloma response, which accelerates the clearance of mycobacteria. Therefore, endogenous IL-10 attenuates mycobacterial immunity.

Effects of whole-body UVB irradiation on cytokine production by peripheral blood mononuclear cells from stage I melanoma patients.

Ultraviolet (UV) radiation causes significant impairment of immunological function in human skin. The immunosuppressive effects of UV radiation are thought to be due to local release of cytokines by human keratinocytes, leading to impaired function of epidermal antigen-presenting cells (APC) and failure to induce cutaneous delayed-type hypersensitivity (DTH) reactions. Recent studies have shown that individuals susceptible to UV-induced suppression of DTH may be more prone to develop skin cancer including malignant melanoma (MM). Since the causal relationship between UV radiation and the induction of MM still seems obscure, we investigated the immunological reactions of peripheral blood mononuclear cells (PBMC) to whole-body irradiation with UVB in 15 stage I melanoma patients as compared to PBMC from normal volunteers matched for age, gender and skin type. Whole-body irradiation was performed with 0.8 minimal erythema dosages on five consecutive days. Peripheral blood was obtained before and after the procedure. Overall, there were no major effects of UVB irradiation on peripheral lymphocyte subsets and proliferation of PBMC from patients or normal controls, but UVB irradiation led to a significant increase in PWM-stimulated production of IL-6, IL-2R and TNF by PBMC. These changes were independent of the individual UVB dosages administered and appeared in both groups similarly. UVB irradiation did not lead to significant changes on IL-1 and IL-2 expression by PBMC. Our results suggest that PBMC participate in the cytokine response to UV, even in the absence of inflammatory reactions, but that this participation is not specific to MM patients.

Effects of Lighting Conditions and Melatonin Supplementation on the Cellular and Humoral Immune Responses in Japanese Quail Coturnix coturnix japonica

Two experiments were conducted to determine the effects of lighting conditions and melatonin supplementation on the cellular and humoral immune responses in Japanese quail. The first experiment was designed to evaluate differing light regimes as immune modulators in both adult and juvenile quail. The cellular and humoral immune responses were determined for three lighting conditions; short days (8:16LD), long days (16:8LD), and constant light (LL). In the second experiment, melatonin was administered in varying doses to adult quail placed in LL. The doses used in this experiment were 0.0, 0.5, 5.0, and 50.0 μg/ml melatonin given in the drinking water for 16 h per day for 2 weeks. The cellular and humoral immune responses were evaluated after 1 week of melatonin treatment. In both experiments, a cutaneous basophil hypersensitivity reaction to phytohemagglutinin (PHA-P) was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were calculated 7 days postintravenous injection with a Chukar red blood cell suspension. In the adult birds of experiment 1, both the 8:16LD and 16:8LD treatments produced similar cellular and humoral immune responses but these responses were significantly greater than those observed in LL. The juvenile birds held under 8:16LD also had significantly greater cellular and humoral immune responses as compared to juvenile birds held in LL. In experiment 2, there was a clear melatonin dose response on immune function in LL. The humoral immune response increased to a peak at the 5.0 μg/ml dose while the cellular immune response increased across all dose levels. From the present study it was clear that quail placed in daily light-dark cycles (LD), possessing a diurnal rhythm of melatonin, had significantly elevated immune responses as compared to those birds in LL. Furthermore, melatonin supplemented to birds exposed to LL was immuno-enhancing. This suggests that melatonin may be a mediator of the differences seen between LD and LL lighting conditions and may have important immune modulating properties.

Impaired leukotriene C4 generation in granulocytes from protein-energy malnourished chronically ill elderly.

The dysregulation of the immune and inflammatory systems observed in protein-energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium ionophore A23187-induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in isolated granulocyte suspensions. Case-control study. A university-affiliated acute care hospital in urban Stockholm. Fourteen severely malnourished elderly subjects with stable non-malignant disorders (age 74 +/- 1 years, mean +/- SEM) and 12 healthy age-matched controls were examined. Leukotrienes were analysed by high-performance liquid chromatography. Body mass index (BMI, kg m-2) and delayed cutaneous hypersensitivity (DCH) reaction were determined. BMI was 16. 5 +/- 0.5 and 26.2 +/- 0.9 kg m-2 (mean +/- SE) in the malnourished group and controls (P < 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5 mm in controls (P < 0.001). LTC4 generation in granulocytes from PEM patients was half of that of controls (9.1 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL-1, P < 0.05) when cells were stimulated with 0.2 micromol L-1 of A23187, and 13.7 +/- 2.5 and 27.2 +/- 7.5 pmol mL-1, respectively (NS), upon stimulation with 1.0 micromol L-1 of A23187. LTB4 production in PEM patients and controls did not differ at any of the two calcium ionophore concentrations. LTC4 production correlated with BMI (r = 0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or LTC4 production. Protein-energy malnutrition is accompanied by perturbation of leukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.

Characterization of an 84 kDa protein inducing an immediate hypersensitivity reaction in rabbits sensitized to Haemaphysalis longicornis ticks

An immunogenic 84 kDa protein was isolated and purified from whole tick extracts of Haemaphysalis longicornis larvae by a combination of ion exchange, reverse phase and hydrophobic interaction chromatographies. The protein, when injected intradermally into rabbits exposed to repeated tick feeding, induces an immediate cutaneous hypersensitivity reaction. It has been purified to homogeneity as shown by sodium dodecyl sulphate polyacrylamide gel electrophoresis and silver staining. Amino acid sequences for two peptides derived from proteolytic cleavage of p84 were scanned against known proteins on the SWISS-PROT database. A 7 residue motif, ISGWGNT present in one of the two peptides appeared conserved in both vertebrate and invertebrate trypsin-like serine proteinases, while another 7 amino acid motif, HVPAGQI present in the second peptide showed homology to an Escherichia coli ATP-binding protein. We have discussed our findings in relation to isolation and characterization of target antigens for tick vaccine candidates.

Use of induced cutaneous immediate-type hypersensitivity reactions to evaluate anti-inflammatory effects of triamcinolone topical solution in three dogs.

The anti-inflammatory effect of a triamcinolone topical solution (TTS) was evaluated by use of induced cutaneous immediate-type hypersensitivity reactions in dogs. Healthy dogs (n = 3) were treated on one side of the lateral thorax with TTS, and on the contralateral side with vehicle solution. After 7 days of treatment, serial dilutions of inflammatory stimuli (histamine, compound 48/80, anticanine IgE, substance P, and morphine sulphate) were injected intradermally on both sides. Resulting immediate reactions were subjectively scored, their diameters were measured in millimetres, and microcirculatory blood flow at each site was measured using laser Doppler velocimetry. The magnitude of the differences between TTS and vehicle-treated sides varied with the type of measurement and the stimulus used. With compound 48/80, anti-IgE, substance P, and morphine sulphate-injected sites, for at least one concentration, the reaction scores and sizes were notably less on the TTS-treated sides. Punch skin biopsy specimens were obtained from selected sites 24 h after injection. A pathologist examined stained tissue sections and scored each section as to degree of late-phase dermal cellular infiltrate. Dermal infiltrate scores were generally lower at the TTS-treated sites; the composite score from all TTS-treated sites was 30% lower than that from the vehicle-treated sites. Observations suggest that TTS may be effective in decreasing some aspects of the inflammatory response in canine skin.

Increased Susceptibility to Immunologically Mediated Glomerulonephritis in IFN-γ-Deficient Mice

Abstract It is postulated that IFN-γ confers susceptibility to immunologically mediated tissue injury. To test this hypothesis, we compared the intensity of accelerated anti-glomerular basement membrane glomerulonephritis between wild-type (IFN-γ+/+) and IFN-γ gene knockout (IFN-γ−/−) mice. This disease model is initiated by binding of heterologous (sheep) anti-glomerular basement membrane Abs to the glomeruli of mice preimmunized with sheep IgG. The secondary cellular and humoral immune responses to the planted Ag then lead to albuminuria and glomerular pathology. We found that IFN-γ−/− mice or IFN-γ+/+ mice injected with IFN-γ-neutralizing Ab develop worse albuminuria and glomerular pathology than IFN-γ+/+ mice. The humoral response to sheep IgG (serum mouse anti-sheep IgG titers and intraglomerular mouse IgG deposits) was comparable in the IFN-γ+/+ and IFN-γ−/− groups. In contrast, IFN-γ−/− mice mounted a stronger cellular immune response (cutaneous delayed-type hypersensitivity reaction) to sheep IgG than IFN-γ+/+ mice. These findings provide evidence that endogenous IFN-γ has a protective role in immunologically mediated glomerulonephritis initiated by foreign Ags.

Nevirapine-induced cutaneous hypersensitivity reactions and successful tolerance induction

Nevirapine-induced cutaneous hypersensitivity reactions and successful tolerance induction

Cutaneous delayed-type hypersensitivity reactions in smokers with chronic bronchitis and recurrent exacerbations: comparison with asymptomatic smokers and never-smokers

The aim of the present study was to investigate whether smoking patients with chronic bronchitis (CB) and recurrent exacerbations show signs of depressed cell-mediated immunity (CMI), as reflected in the cutaneous delayed-type hypersensitivity (DTH) reaction, in comparison with asymptomatic smokers and healthy never-smokers. The study was a comparative clinical study performed at a university hospital center of respiratory medicine. Sixteen smokers with stable CB and recurrent exacerbations, five of whom had mild airflow obstruction, 18 asymptomatic smokers and 18 healthy never-smokers, all aged between 35 and 64 years, participated. No subjects treated with corticosteroids or N-acetylcysteine were included. Cutaneous DTH-reactions to seven recall antigens were assessed with Multitest ®, a standardized in vivo test of clinical CMI. Reactions were assessed 48 h after application by measurement of skin induration. A score (sum in mm of positive reactions) was created to assess overall reactivity. Neither the score nor the number of positive reactions differed significantly between the three study groups. Men had a significantly higher reactivity than women ( P<0.05) irrespective of group affiliation. No influence of smoking status on DTH reactivity could be seen. In the CB group no correlation was found between DTH reactivity and number of exacerbations the past 2 years. Patients with chronic bronchitis and recurrent exacerbations did not differ from asymptomatic smokers or healthy never-smokers with respect to cutaneous DTH reactions. Depression of CMI, as measured in this study, does not seem to be a primary factor behind recurrent exacerbations in smokers with CB.

A new concept of skin-associated lymphoid tissue (SALT): UVB light impaired cutaneous immunity reveals a prominent role for cutaneous nerves.

More than 20 years have passed since the concept that the skin has its own associated immune system was first proposed by Streilein. This proposal was advanced in part on evidence that cutaneous contact hypersensitivity (CH) reactions are closely correlated with Langerhans cells (LC). Recent reports have demonstrated that LC have neural connectivity with cutaneous nerve termini containing calcitonin gene-related peptide (CGRP), suggesting that a link exists between innervation and immune responses in the skin. Here we discuss the neural components which have recently been found to be participants in skin-associated lymphoid tissue (SALT). In part, discovery of a functional link between the nervous system and SALT is based on studies in which cutaneous immunity was impaired by ultraviolet-B radiation (UVR). The deleterious effects of UVR on cutaneous immunity include failed CH induction and promotion of hapten-specific tolerance, effects that are mediated by tumor necrosis factor-alpha and interleukin-10, respectively. The source of these cytokines after UVR appears to be dermal mast cells. Evidence indicates that mast cells are triggered to release these cytokines in response to CGRP, which is released from UVR-damaged cutaneous nerve endings. Moreover, a substance P agonist was able to reverse the deleterious effects of UVR on CH induction, rendering the mice able to develop intense CH. These observations indicate that two cell types not originally included in the SALT concept are critical to the functional integrity of cutaneous immunity: mast cells and cutaneous nerves. We propose that cutaneous nerves dictate whether antigen applied to or arising within skin will lead to sensitivity or tolerance.

Quantitative Assessment of Immediate Cutaneous Hypersensitivity in a Model of Genetic Predisposition to Atopy

Genetic predisposition and environmental factors modulate the expression of allergic phenotypes. The frequent allergic phenotype 'immediate cutaneous hypersensitivity' was established in mice as a model for atopy. Genetic dissection of this trait requires a robust procedure to assess the allergic phenotype. To this end, different mouse strains were immunized with birch pollen extract. Immediate cutaneous hypersensitivity reactions were induced through intradermal allergen exposure. Wheel formation was quantitated and expressed as a hypersensitivity score according to the bonitur method. This procedure identified A/J and C57BL/6 mice as high– and low–responder strains, respectively. Crosses of A/J and C57BL/6 mice should allow the characterization of mendelian factors responsible for the two extreme phenotypes identified here.

BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model

Background: Epidemiologic studies suggest an inverse correlation between infections and development of atopy. The purpose of this study was to test the hypothesis whether a preexisting T h 1 -type immune response elicited by BCG immunization could suppress allergic sensitization and airway hyperreactivity in an animal model. Methods: BALB/c mice were immunized with BCG and/or sensitized to ovalbumin. Results: BCG immunization alone resulted in cutaneous type-IV hypersensitivity reactions to tuberculin and granulomatous lesions in the liver. Splenic mononuclear cells (MNCs) produced increased levels of IFN-γ after activation by Concanavalin A (ConA). Ovalbumin sensitization alone resulted in increased production of IL-4 after activation by ConA. Ovalbumin-sensitized animals also demonstrated markedly elevated anti-ovalbumin IgE/IgG1 serum antibody titers and increased airway reactivity after allergen challenges by means of the airways. BCG immunization 14 days before the start of ovalbumin sensitization markedly hindered the development of allergic responses as indicated by (1) increased IFN-γ and normalized IL-4 and IL-10 production by splenic MNCs after activation with ConA, (2) a reduced proliferation rate of splenic MNCs after ovalbumin restimulation, (3) partial prevention of ovalbumin-specific IgE/IgG1 serum antibody titers but elevated (nonallergic) anti-ovalbumin IgG2a serum antibody titers, (4) prevention of airway responsiveness, (5) reduced eosinophilic influx into the airway lumen, and (6) reduced levels of IL-4 and IL-5 in broncho alveolar lavage fluids. Conclusion: In this model BCG immunization established a T h 1 -type immune response that hinders allergic sensitization and the development of increased airway reactivity. (J Allergy Clin Immunol 1998;102:867-74.)

Quantitative immunohistochemical differences in Langerhans cells in dermatitis due to internal versus external antigen sources

Cutaneous hypersensitivity reactions can develop against antigens delivered through the epidermis (contact dermatitis) or through the blood vessels (e.g., drug eruptions). On routine histology alone, it is not always possible to determine the route of the antigen. Langerhans cells (LC) are the main antigen-presenting cells in contact dermatitis. Dermal dendrocytes (DC) are antigen-presenting cells and may be involved in dermal reactions. We tested the hypothesis that there is a difference between dermatitis due to external and internal antigen sources with regard to the number or function of LC and DC. In 85 cases of dermatitis, numbers of S100 and HLA-DR reactive cells per linear millimetre of epidermis were counted. The amount of epidermal spongiosis was evaluated qualitatively. In 35 cases, the number of DC per mm2 (as defined by Factor XIIIa expression) was evaluated. The patients were then divided into two groups based on whether the final clinical evaluation considered the dermatitis to be secondary to an external (35 cases) or internal antigen (50 cases). Dermatitis due to external antigens had significantly more LC/mm and more frequent HLA-DR expression than dermatitis due to internal antigens, mean +/- SEM; 21.2+/-2.04 vs. 9.1+/-1.02 (p<0.00001) and 16.3+/-2.49 vs. 6.0+/-0.92 (p=0.0001), respectively. Spongiosis was more marked in external antigen cases. DC were more numerous in internal than in external antigen cases, but the differences were not statistically significant. In our model, determination of numbers of LC/mm is the variable with the highest power to discriminate between internal and internal sources. Quantification of HLA-DR+ LC and degree of spongiosis provide little additional discriminatory power.

Various immunological phenotypes are associated with increased airway responsiveness.

Bronchial asthma is characterized by a TH2 type immune response, chronic inflammation of the airways and increased airway responsiveness. The relationship between IgE- and inflammatory-dependent mechanisms that contribute to bronchial asthma are not well defined. The purpose of this study was to compare and analyse the immune pathways that resulted in development of allergen-induced and/or inflammatory dependent increased airways responsiveness. BALB/c and C57BL/6 mice responded to OVA-sensitization with elevated allergen-specific IgE/IgG1 serum antibody-titres and the development of cutaneous immediate-type hypersensitivity reactions. Increased airway responsiveness was observed following airway allergen challenges. However, the inflammatory component of the lung differed between the strains. In OVA-sensitized BALB/c mice a marked increase in lymphocytes, eosinophils and neutrophils in BAL fluids was parallelled with elevated production of IL-4, IL-5 and TNFalpha in the lung. In contrast in OVA-sensitized C57BL/6 mice, the inflammatory immune response in the lung was much weaker. We postulate that two pathways can regulate the induction of increased airway responsiveness. One depends on the presence of allergen-specific IgE/IgG1 and allergen, and a second is mediated by allergen-independent inflammation of the lung. To test this hypothesis, BALB/c mice were treated nasally with low doses of bacterial superantigen (SEB) as a prototypical inducer of airway inflammation, following which influx of lymphocytes, eosinophils and neutrophils into the airways was parallelled by development of increased airway-responsiveness in the absence of allergen-specific IgE/IgG1 antibodies and allergen. These results indicate that increased airway responsiveness is associated with different immunological phenotypes in BALB/c and C57BL/6 mice.

Gout in the elderly. Clinical presentation and treatment.

Gout in the elderly differs from classical gout found in middle-aged men in several respects: it has a more equal gender distribution, frequent polyarticular presentation with involvement of the joints of the upper extremities, fewer acute gouty episodes, a more indolent chronic clinical course, and an increased incidence of tophi. Long term diuretic use in patients with hypertension or congestive cardiac failure, renal insufficiency, prophylactic low dose aspirin (acetylsalicylic acid), and alcohol (ethanol) abuse (particularly by men) are factors associated with the development of hyperuricaemia and gout in the elderly. Extreme caution is necessary when prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute gouty arthritis in the elderly. NSAIDs with short plasma half-life (such as diclofenac and ketoprofen) are preferred, but these drugs are not recommended in patients with peptic ulcer disease, renal failure, uncontrolled hypertension or cardiac failure. Colchicine is poorly tolerated in the elderly and is best avoided. Intra-articular and systemic corticosteroids are increasingly being used for treating acute gouty flares in aged patients with medical disorders contraindicating NSAID therapy. Urate-lowering drugs are indicated for the treatment of hyperuricaemia and chronic gouty arthritis. Uricosuric drugs are poorly tolerated and the frequent presence of renal impairment in the elderly renders these drugs ineffective. Allopurinol is the urate-lowering drug of choice, but its use in the aged is associated with an increased incidence of both cutaneous and severe hypersensitivity reactions. To minimise this risk, allopurinol dose must be kept low. A starting dose of allopurinal 50 to 100mg on alternate days, to a maximum daily dose of about 100 to 300mg, based upon the patient's creatinine clearance and serum urate level, is recommended. Asymptomatic hyperuricaemia is not an indication for long term urate-lowering therapy; the risks of drug toxicity often outweigh any benefit.

Delayed migration of Plasmodium sporozoites from the mosquito bite site to the blood.

Studies were done on delivery of Plasmodium yoelii sporozoites by Anopheles stephensi into the skin of BALB/C mice. When infected mosquitoes fed on a portion of the ear, 81% of these positive control mice developed parasitemia. When the fed-upon site was excised immediately or 5 min postfeeding, a highly significant, smaller percentage of these experimental mice developed parasitemia. When the delay in removal of mosquito-bitten tissue was extended to 15 min, no significant difference was found between this group and positive control mice. These findings show that mosquito-injected sporozoites tend to remain at the bite site for at least 5 min after the mosquito bite. By approximately 15 min, the first wave of migrating sporozoites has left the bite site and moved into the general circulation. These findings have implications concerning possible host obstruction of sporozoite migration in skin by either anti-sporozoite antibodies or by a cutaneous hypersensitivity reaction to mosquito bite.

Endothelial Cells Implicated in Delayed Hypersensitivity Reactions

The pathogenesis of cutaneous delayed hypersensitivity reactions is not yet fully understood. While circulating lymphocytes and their resultant

Immunologic determinants of susceptibility to experimental glomerulonephritis: Role of cellular immunity

To identify the immunologic mechanisms that influence susceptibility to GN, we compared the severity of accelerated anti-glomerular basement membrane (GBM) nephritis between Lewis (LEW) and Brown Norway (BN) rats and analyzed differences in their immune responses to the nephritogenic immunoglobulin. Lewis (LEW) rats preimmunized with sheep IgG developed proliferative GN with marked proteinuria [peak protein excretion (mean +/- SEM) = 85.3 +/- 15.3 mg/24 hr; normal = 6.4 +/- 0.8 mg/24 hr] after receiving a subnephritogenic dose of sheep anti-rat GBM antiserum. Identically treated Brown Norway (BN) rats, on the other hand, had minimal renal pathology and minimal proteinuria (peak protein excretion = 22.6 +/- 3.1 mg/24 hr; normal = 13.0 +/- 0.6 mg/24 hr). Serum titers of rat anti-sheep IgG isotypes and intraglomerular binding of sheep IgG, rat IgG, and rat complement (C3) were comparable in both strains. In contrast, only LEW rats developed a strong cellular immune response to sheep IgG represented by intrarenal T lymphocyte (OX19+) and monocyte (ED1+) accumulation [LEW vs. BN (mean +/- SEM): OX19+ = 0.60 +/- 0.10 vs. 0.14 +/- 0.01 cells/glomerulus, control = 0.02 +/- 0.01; ED1+ = 4.0 +/- 0.4 vs. 1.0 +/- 0.2 cells/glom., control = 0.8 +/- 0.3] and a significant cutaneous delayed-type hypersensitivity (DTH) reaction [LEW versus BN (mean +/- SEM): delta ear thickness = 0.22 +/- 0.02 vs. 0.05 +/- 0.03 mm; control = 0.04 +/- 0.02 mm]. Upon rechallenge with sheep IgG in vitro, LEW splenocytes expressed a T helper 1 (Th1) cytokine pattern (IFN gamma and IL-2 mRNA, but little IL-4 mRNA) which is associated with delayed-type hypersensitivity reactions. BN splenocytes, on the other hand, expressed IL-4 in addition to IL-2 and IFN gamma mRNA that is consistent with an undifferentiated (Th0) cytokine profile. These studies suggest that humoral immunity to heterologous immunoglobulin planted in the kidney is not sufficient for full expression of accelerated anti-GBM nephritis, and that additional cellular immune mechanisms are required. We conclude that susceptibility to accelerated anti-GBM nephritis is strongly influenced by the host's propensity to mount a Th1-type response and DTH reaction to the disease-inciting immunoglobulin.

Persistent cutaneous hypersensitivity reaction after a Hawaiian box jellyfish sting (Carybdea alata)

Persistent cutaneous hypersensitivity reaction after a Hawaiian box jellyfish sting (Carybdea alata)