Tunable non-integer high-harmonic generation in a topological insulator.

When intense lightwaves accelerate electrons through a solid, the emerging high-order harmonic (HH) radiation offers key insights into the material1-11. Sub-optical-cycle dynamics-such as dynamical Bloch oscillations2-5, quasiparticle collisions6,12, valley pseudospin switching13 and heating of Dirac gases10-leave fingerprints in the HH spectra of conventional solids. Topologically non-trivial matter14,15 with invariants that are robust against imperfections has been predicted to support unconventional HH generation16-20. Here we experimentally demonstrate HH generation in a three-dimensional topological insulator-bismuth telluride. The frequency of the terahertz driving field sharply discriminates between HH generation from the bulk and from the topological surface, where the unique combination of long scattering times owing to spin-momentum locking17 and the quasi-relativistic dispersion enables unusually efficient HH generation. Intriguingly, all observed orders can be continuously shifted to arbitrary non-integer multiples of the driving frequency by varying the carrier-envelope phase of the driving field-in line with quantum theory. The anomalous Berry curvature warranted by the non-trivial topology enforces meandering ballistic trajectories of the Dirac fermions, causing a hallmark polarization pattern of the HH emission. Our study provides a platform to explore topology and relativistic quantum physics in strong-field control, and could lead to non-dissipative topological electronics at infrared frequencies.

Super-resolution lightwave tomography of electronic bands in quantum materials.

Searching for quantum functionalities requires access to the electronic structure, constituting the foundation of exquisite spin-valley-electronic, topological, and many-body effects. All-optical band-structure reconstruction could directly connect electronic structure with the coveted quantum phenomena if strong lightwaves transported localized electrons within preselected bands. Here, we demonstrate that harmonic sideband (HSB) generation in monolayer tungsten diselenide creates distinct electronic interference combs in momentum space. Locating these momentum combs in spectroscopy enables super-resolution tomography of key band-structure details in situ. We experimentally tuned the optical-driver frequency by a full octave and show that the predicted super-resolution manifests in a critical intensity and frequency dependence of HSBs. Our concept offers a practical, all-optical, fully three-dimensional tomography of electronic structure even in microscopically small quantum materials, band by band.

The disease modifying osteoarthritis drug diacerein is able to antagonize pro inflammatory state of chondrocytes under mild mechanical stimuli.

OBJECTIVE: To investigate the combination of mild mechanical stimuli and a disease modifying osteoarthritis drug (DMOAD) in inflammatory activated chondrocytes and to study the combination of drug and mechanical tension on the cellular level as a model for an integrated biophysical approach for osteoarthritis (OA) treatments. METHODS: Interleukin-1beta (IL-1ß) stimulated C28/I2 cells underwent mild mechanically treatment while cultured in the presence of the DMOAD diacerein. The pharmacological input of diacerein was evaluated by cell viability and cell proliferation measurements. Inflammation and treatment induced changes in key regulatory proteins and components of the extracellular matrix (ECM) were characterized by quantitative real-time PCR (qPCR). The effects on metalloproteinase-1 (MMP-1) activity and glycosaminoglycan (GAG) concentration in cell supernatants of treated cells were investigated. RESULTS: C28/I2 cells demonstrated significant changes in expression of inflammatory and cartilage destructive proteins in response to IL-1ß stimulation. The chondroprotective action of diacerein in mechanically stimulated cells was mediated by a decrease in interleukin-8 (IL-8), fibronectin-1 (FN-1), collagen type I (Col 1) and MMP-1 expression levels, respectively. Augmented expression of interleukin-6 receptor (IL-6R) and the fibroblast growth factor receptors (FGFRs) by diacerein was not abolished by mechanical treatment. The observed effects were accompanied by a reduced cell proliferation rate, attenuated cell viability and extenuated MMP-1 activity. CONCLUSION: Diacerein diversely regulates the expression of main regulatory proteins as well as components important to regenerate and set up ECM. Mechanical stimulation does not negatively influence the chondroprotective effect induced by diacerein treatment in immortalized human C28/I2 chondrocytes.

[Allergies in adults]. / Allergien bei Erwachsenen.

Only few epidemiological studies have assessed allergic diseases in adults. In a follow-up study of the MONICA survey S3 (1994/95), which was performed 1997-1999, a total of 1,537 persons were interviewed and tested by skin prick and patch test. Furthermore data of the MONICA survey (RAST, cholesterol, food diaries) could be used. Within survey S4 (1999/2001) a total of 4,261 subjects were interviewed concerning their personal history of atopic diseases and the corresponding history of their partners. In survey S3 the prevalence of allergic sensitisation was 20.5 % for persons without formal graduation from school and 48.1 % for those with a university degree. 20.8 % reported a hypersensitivity to food and about one quarter exhibited a positive reaction in skin prick test. Atopic eczema and hay fever increased over quartiles of HDL cholesterol. Similar, allergic sensitisation (RAST) increased over quartiles of uptake of unsaturated fatty acids in men. 40 % of those who were patch tested exhibited a positive reaction, with perfume mix, nickel, thimerosal and balsam of Peru being the most prominent allergens. Inhabitants of the City of Augsburg were sensitised more often (34.0 % overall, 23.9 % pollen) than inhabitants of villages with (29.4 %, 17.0 %). Full time farmers were sensitised less frequently (22.0 %, 8.4 %). In survey S4 the lifetime prevalence of atopic diseases diagnosed by doctors was 5.1 % for atopic eczema, 6.1 % for asthma and 13.7 % for hay fever. Subjects who lived together with a partner who suffered from hay fever were affected in 19.6 % whereas 13.1 % had hay fever when the partner was not affected. Future studies will offer an unique opportunity to analyse the incidence and remission of manifestations of atopy in adults.

Intake of unsaturated fatty acids and HDL cholesterol levels are associated with manifestations of atopy in adults.

BACKGROUND: The increase in allergic diseases is still unexplained. It was hypothesized that the intake of unsaturated fatty acids is a contributing cause of this development. We investigated the relationship between serum cholesterol levels, intake of polyunsaturated fatty acids (PUFA) and manifestations of atopy in a population-based setting. METHODS: A nested case-control study was performed within the population of the 3rd MONICA survey in Augsburg (Germany). The serum levels of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol of 1537 adults (aged 28-78 years, response 61.4%) and the estimated intake of PUFA in a subset of 139 men were compared with the frequency of a doctor's diagnosis of asthma, allergic rhinoconjunctivitis (AR), atopic eczema (AE) and allergic sensitization as measured by skin prick and Radio Allergo Sorbent Test. FINDINGS: In bivariate analyses, we obtained a negative linear association between total and LDL cholesterol levels and the frequency of AR and sensitization, which was no longer significant after adjustment for important confounders. In contrast, positive linear associations were found between HDL cholesterol levels and AR and AE and, furthermore, between the intake of PUFA and allergic sensitization in men (P<0.01). After adjustment, an increasing risk for atopic diseases with increasing levels of HDL cholesterol and an increasing risk for allergic sensitization with increasing intakes of PUFA remained statistically significant. INTERPRETATION: There is indication that HDL cholesterol also plays a role in the complex interaction of fat intake, metabolism and the manifestation of atopy in adults. These findings may contribute to the understanding of time trends and regional differences of allergies.

[Recurrent palmoplantar hidradenitis in childhood]. / Die rekurrierende palmoplantare hidradenitis im Kindesalter.

We describe five cases of recurrent palmoplantar hidradenitis in children. The pathogenesis of this highly characteristic disease presenting with painful erythematous papules and nodules involving palms of the hands, soles of the feet, or both is not clear at the moment. One possible mechanism is a temporal relationship between exposure to dampness and cold, which also applied in four of these children. The self-limited disease tends to reappear. After thoroughly informing the children and their parents on avoiding provoking factors, all children experienced freedom from the disease during a 12-month follow-up.

Epidemiology of food allergy/food intolerance in adults: associations with other manifestations of atopy.

BACKGROUND: Food allergy and food intolerance (FA/FI) are believed to be frequent medical problems; however, information from epidemiologic studies in adults is scarce. The objective was to determine the frequency of FA/FI and allergic sensitization to food in a large adult sample. Furthermore, the associations between FA/FI and other outcomes of atopy were studied. METHODS: Within a population-based, nested, case-control study, a standardized interview was performed to obtain detailed information on FA/FI and the history of atopic diseases. In addition, a skin prick test with 10 common food and nine aeroallergens was performed. RESULTS: Overall, 20.8% of the 1537 studied subjects (50.4% female, age median 50 years) reported FA/FI (women 27.5%, men 14.0%; OR 2.35, CI 1.80-3.08). Nuts, fruits, and milk most frequently led to adverse effects, and the sites of manifestation were oral (42.9%), skin (28.7%), gastrointestinal (13.0%), systemic (3.2%), and multiple (12.2%). One-quarter of the subjects (25.1%) were sensitized to at least one food allergen in the prick test, with hazelnut (17.8%), celery (14.6%), and peanut (11.1%) accounting for most of the positive reactions. The corresponding frequency estimates for the representative study base (n=4178) were 15.5% for reported adverse reactions and 16.8% for allergic sensitization. Relevant concomitant sensitization to food and aeroallergens was observed. Food-allergic subjects (positive history and sensitization to corresponding allergen) suffered significantly more often from urticaria, asthma, atopic eczema, and especially hay fever (73.1%) than controls (3.0%). Furthermore, hay fever was treated significantly more often in subjects who suffered from concomitant food allergy. CONCLUSIONS: FA/FI in adults is frequently reported and associated with other manifestations of atopy. Hay fever in conjunction with FA/FI tends to be clinically more severe since therapeutic needs are enhanced.

Epidemiology of contact allergy in adults.

BACKGROUND: We aimed to determine the prevalence of contact sensitization in the general population and to investigate associations with important sociodemographic and medical characteristics. METHODS: Within a population-based nested, case-control study in Germany, we performed patch tests with 25 standard allergens in 1141 adults (50.4% female, age median 50 years). Additional information was obtained by a dermatologic examination, a standardized interview, and blood analysis. RESULTS: At least one positive reaction was exhibited by 40.0% of the subjects, with reactions most frequently observed to fragrance mix (15.9%), nickel (13.1%), thimerosal (4.7%), and balsam of Peru (3.8%). Women were sensitized more often than men (50.2% vs 29.9%, OR 2.36, CI 1.84-3.03), and this was also significant for fragrance mix, nickel, turpentine, cobalt chloride, and thimerosal. Contact sensitization was more frequent in subjects who reported adverse skin reactions (53.8% vs. 32.6%; OR 2.41, CI 1.85-3.14), and this was particularly true for sensitization to nickel (45.5% vs 8.8%, OR 8.64, CI 5.67-13.17) and fragrance mix (29.0% vs 14.0%, OR 2.51, CI 1.60-3.91) and the corresponding intolerance of fashion jewelry and fragrances. Contact sensitization decreased with increasing degree of occupational training (unskilled 45.9%, apprenticeship 40.1%, technical college 40.4%, and school of engineering 12.5%; P=0.023; trend test P=0.042). Significant associations of contact sensitization and presence of allergen-specific IgE antibodies, atopic eczema, or psoriasis were not observed. Frequency estimates for the general adult population based on these findings were 28.0% for overall contact sensitization and 11.4% for fragrance mix, 9.9% for nickel, and 3.2% for thimerosal. CONCLUSIONS: It is concluded that contact allergy is influenced by sociodemographic parameters and plays an important role in the general population.

School education and allergic sensitization in adults.

BACKGROUND: There is evidence of an association between socioeconomic status (SES) and atopy mainly from studies in children which investigated atopic diseases and parental SES. We determined the association of allergic sensitization, as measured by skin prick test (SPT) and allergen-specific IgE (RAST), and SES in a population-based study in adults. METHODS: Within a population-based, nested, case-control study, a standardized interview was performed and allergic sensitization to common aeroallergens was determined by SPT and RAST. RESULTS: A total of 1537 adults (50.4% female, age: median 50.0, range 28-78 years) were investigated, half of whom (50.2%) exhibited at least one positive RAST result according to the study design. SPT reactivity was 37.3% in this group and was estimated to be 26.1% in the representative study base of 4178 adults. Within increasing categories of school graduation (none; after 8, 10, 13, and >13 years), the prevalence of SPT (20.5%, 31.3%, 44.0%, 44.2%, 48.1%; P trend <0.0001) and RAST reactivity (35.0%, 48.0%, 52.3%, 48.4%, 58.4%; P trend=0.004) increased continuously. Similar results were obtained when testing this association on the level of single allergens. After control for age, sex, and parental history of atopic diseases, all but the first odds ratios for SPT remained significant (first category=reference, 2.06, 3.21, 3.88, 3.96). The same model for RAST reactivity revealed a similar result with effect estimate for the last category being significant (first category=reference, 1.89, 2.08, 2.10, 2.81). CONCLUSIONS: Allergic sensitization (SPT and RAST) to common aeroallergens in adults follows a significant and linear association with school education.

[Confluent and reticulate papillomatosis. Successful therapy with azithromycin]. / Papillomatosis confluens et reticularis. Erfolgreiche Therapie mit Azithromycin.

Confluent and reticulated papillomatosis is a fairly rare dermatosis of still unknown origin affecting mostly female young adults. The lesions are mainly localized in the midline of the trunk. Systemic treatment is the treatment of choice because the disease is resistant to topical therapy and recurrences are often seen. In recent publications retinoids and minocycline have been reported as the favourite therapeutic approaches. We successfully treated a 19-year-old-girl with azithromycin resulting in a complete healing of all skin lesions. The patient has been free of disease for five months. Based on our own case and data in literature, azithromycin is an effective, reasonable and safe therapeutic alternative.

G protein-gated inwardly rectifying potassium channels are targets for volatile anesthetics.

G protein-gated inwardly rectifying potassium channels (GIRKs) are a family of homo- and hetero-oligomeric K(+) channels composed of different subunits (GIRK1 to 4 in mammals). GIRK4 and GIRK1 are found mainly in the atrium, whereas neuronal cells predominantly express the GIRK1, GIRK2, and GIRK3 isoforms. When activated, GIRK channels slow the firing rate of atrial myocytes and neuronal cells. Because of their key role in controlling excitability, we investigated the influence of a prototypic anesthetic, halothane, on GIRK channels of different subunit composition expressed in Xenopus laevis oocytes. Halothane enhanced background currents through hetero-oligomeric GIRK1/GIRK4 and homo-oligomeric GIRK1(F137S) channels but not through homo-oligomeric GIRK2 channels. This activation of basal current did not depend on the presence of coexpressed G protein-coupled receptors but instead required the presence of G(beta/gamma). In contrast to basal GIRK currents, the agonist-induced GIRK current (via coexpressed m2 muscarinic receptors) was inhibited by halothane. For GIRK1/GIRK4 and GIRK1(F137S) channels this inhibition was most pronounced at low concentrations of the anesthetic (0.1-0.3 mM) and occurred also when channels had been activated by guanosine-5'-O-(3-thio)triphosphate. This inhibition, however, was overridden by high concentrations of halothane (0.9 mM) and augmentation of the agonist-induced current was observed. This increase in agonist-induced current was never seen with GIRK2 homo-oligomeric channels. Agonist-induced currents mediated by GIRK2 channels were always inhibited by halothane with an IC(50) value of approximately 60 microM. These data suggest a direct interaction of halothane with GIRK channels.

Food intake of patients with atopic dermatitis.

There is only restricted information about the nutritional behavior of adult patients with atopic dermatitis (AD). Our purpose was to evaluate the food intake in a series of patients with AD with particular consideration of self-reported food intolerance. Particular attention was paid to the risks of nutrient deficiencies. We examined the intake of 28 food items in 116 AD patients with a food-frequency questionnaire (FFQ). For each food item the cohort was divided in two groups according to whether symptoms were reported or not (symptomatic vs. asymptomatic). We found in a series of food items a significant lower food intake among symptomatic patients. Significantly lower intakes were reported by symptomatic patients for dairy products, fish, egg, pork, oranges, non-specified fruits, apples, kiwis, green or red peppers, peanuts and hazelnuts. We concluded that in symptomatic AD patients supplementation with specific nutrients might become mandatory. This is particularly pertinent for calcium, iodine, vitamin C and n-3 fatty acids.

Optimizing the therapeutic approach in tinea capitis of childhood with itraconazole.

BACKGROUND: Tinea capitis is the most common dermatophytosis of childhood with increasing incidence. Whereas griseofulvin is considered by many as the mainstay of treatment, newer oral antifungal agents, including fluconazole, itraconazole and terbinafine have demonstrated higher efficacy, resulting in shorter treatment durations. OBJECTIVES: We aimed to determine the optimum regimen for the treatment of childhood tinea capitis with itraconazole. METHODS: A mycological culture outcome-dependent combination of a 28-day continuous and facultative additional 14-day courses with itraconazole was used in 42 children (20 girls; 22 boys) aged 12-140 months (mean 66) with tinea capitis due to Microsporum canis (n = 26) and Trichophyton violaceum (n = 16). The drug was given orally according to the patients' body weight (50 mg daily for < 20 kg; 100 mg daily for > or = 20 kg) over 4 weeks. Direct microscopy and fungal culture as a parameter for efficacy were repeated 2 weeks after termination of treatment. Assessment of efficacy was based on the evaluation of results from light microscopy and culture at 8 weeks after initiation of treatment, and in the case of a further positive mycological culture at 14 and 20 weeks, respectively. A positive fungal culture at these times resulted in an additional course for 2 weeks with the initially chosen itraconazole dosage. RESULTS: In 34 of 42 patients a single 4-week course of itraconazole resulted in a complete mycological cure of lesions as demonstrated by light microscopy and mycological culture. Four of 42 patients had to be treated by a second itraconazole course for 2 weeks, and four children received a third course of itraconazole for 2 weeks until all lesions showed negative direct microscopy and mycological culture. No abnormal haematological or biochemical results occurred. Apart from transient, completely reversible indigestion in two children, no side-effects were observed. CONCLUSIONS: A culture-based 28-day continuous therapeutic regimen plus facultative cultural outcome-dependent additional 14-day courses of a body weight-adapted dosage of itraconazole in tinea capitis due to M. canis and T. violaceum is discussed; this offers the advantage of an effective therapy with complete negative direct microscopy as well as negative cultural results, within a shorter active treatment period (cf. previous studies with continuous administration of itraconazole).

Dihydropyridine-induced Ca2+ release from ryanodine-sensitive Ca2+ pools in human skeletal muscle cells.

Dihydropyridines (DHPs) are widely used antihypertensive drugs and inhibit excitation-contraction (E-C) coupling in vascular smooth muscle and in myocardial cells by antagonizing L-type Ca2+ channels (DHP receptors). However, contradictory reports exist about the interaction of the DHP with the skeletal muscle isoform of the DHP receptor and E-C coupling in skeletal muscle cells. Using the intracellular fluorescent Ca2+ indicator fura-2, an increase in [Ca2+]i was observed after extracellular application of nifedipine to cultured human skeletal muscle cells. The rise in [Ca2+]i was dose dependent with a calculated EC50 of 614 +/- 96 nM nifedipine and a maximum increment in [Ca2+]i of 80 +/- 3.2 nM. Similar values were obtained with nitrendipine. This effect of DHPs was restricted to differentiated skeletal muscle cells and was not seen in non-differentiated cells or in PC12 cells. In spite of the observed increase in [Ca2+]i, whole-cell patch clamp experiments revealed that 10 microM nifedipine abolished inward Ba2+ currents through L-type Ca2+ channels completely. Similar to nifedipine, (+/-)Bay K 8644, an agonist of the L-type Ca2+ channel, also increased [Ca2+]i. This effect could not be enhanced by further addition of nifedipine, suggesting that both DHPs act via a common signalling pathway. Based on the specific mechanism of the skeletal muscle E-C coupling, we propose the stabilization of a conformational state of the DHP receptor by DHPs, which is sufficient to activate the ryanodine receptor.

Pharmacological activation of the ryanodine receptor in Jurkat T-lymphocytes.

1 Recently, we provided evidence for cyclic adenosine 5'-diphosphate-ribose, cADP-ribose, as a second messenger in Jurkat T-lymphocytes upon stimulation of the T-cell receptor/CD3- complex (Guse et al., 1999). cADP-ribose mobilizes Ca2+ from an intracellular Ca2+ store which is sensitive to caffeine and gated by the ryanodine receptor/Ca2+ release channel. In the present study we investigated the ability of the trypanocidal drug, suramin, to activate the ryanodine receptor of T-cells. Since suramin cannot permeate the plasma membrane, it was necessary to microinject the drug into Fura-2 loaded T-lymphocytes. 2 In a dose dependent manner suramin increased the intracellular Ca2+ concentration. The dose-response curve is very steep and calculates for an EC50 of 7. 6+/-2.9 mM suramin in the injection pipette. 3 Co-injection of the selective ryanodine receptor inhibitor ruthenium red completely abolished the suramin induced Ca2+ transient. This finding allows for the conclusion that the IP3-receptor sensitive Ca2+ pool is not the primary target of the suramin induced Ca2+ transient. 4 Furthermore, Ins(1,4,6)PS3, an antagonist of the InsP3-receptor could not suppress the suramin-induced Ca2+ signal. The suramin induced Ca2+ transients declined very slowly; however, in the presence of Ins(1,4,6)PS3 this decay was accelerated. In addition, suramin did not interact with the cADP-ribose binding site of the ryanodine receptor of T-cells. 5 In conclusion, suramin is found to be an agonist for the T-cell ryanodine receptor as previously found for the cardiac and skeletal muscle isoform. Therefore, suramin can be designated a universal ryanodine receptor agonist.

Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis.

In allergic inflammations of the skin, activation of CD4+ T cells was demonstrated to play an important role; however, a minor role for CD8+ T cells is implied. In the present study, we compared cutaneous lymphocyte-associated Ag (CLA)-expressing CD4+ and CD8+ subsets, which were isolated from peripheral blood and lesional skin biopsies in atopic dermatitis (AD) patients. We demonstrated that CD8+CLA+ T cells proliferate in response to superantigen and are as potent as CD4+CLA+ T cells in IgE induction and support of eosinophil survival. In atopic skin inflammation, the existence of high numbers of CD4+ and CD8+ T cells was demonstrated by immunohistochemistry and by culturing T cells from skin biopsies. In peripheral blood, both CD4+ and CD8+ subsets of CLA+CD45RO+ T cells were in an activated state in AD. The in vivo-activated CLA+ T cells of both subsets spontaneously released an IL-5- and IL-13-dominated Th2 type cytokine pattern. This was confirmed by intracytoplasmic cytokine staining immediately after isolation of the cells from peripheral blood. In consequence, both CD4+ and CD8+, CLA+ memory/effector T cells induced IgE production by B cells mainly by IL-13, and enhanced eosinophil survival in vitro by delaying eosinophil apoptosis, mainly by IL-5. These results indicate that in addition to the CD4+ subset, the CD8+CLA+ memory/effector T cells are capable of responding to superantigenic stimulation and play an important role in the pathogenesis of AD.

A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production.

Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.

Skin-homing, CLA+ memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA- memory T cells.

Cutaneous lymphocyte-associated Ag (CLA) is a skin-homing receptor displayed by memory/effector T cells recognizing skin-related allergens. Here we demonstrate that peripheral blood CLA+ CD45RO+ T cells in patients with atopic dermatitis (AD) are in vivo activated. They spontaneously proliferate and release an IL-13-dominated Th2 cytokine profile and are capable of inducing IgE in autologous B cells without further activation. The spontaneous cytokine release occurred within the first hour of culture and was not inhibited by cycloheximide or by other immunosuppressive drugs, indicating that cytokine transcription and translation had been completed in vivo. In contrast, the CLA- CD45RO+ T cells from the same patients and from nonatopic controls represented a resting memory T cell subset, secreted borderline quantities of cytokines, and induced IgG4. Polyclonal activation by the anti-CD2/anti-CD3/anti-CD28 mAb mixture generated distinct cytokine patterns in the two memory/effector T cell subsets. CLA+ T cells secreted Th2 cytokines with high IL-13 levels, and the CLA- subset mainly produced IFN-gamma. There was no difference in in vitro activated cytokine pattern between AD patients and nonatopic subjects. These results indicate that the CLA+ memory/effector T cells of AD patients are activated in vivo and play a pivotal role in allergic inflammation by production of IL-13 and induction of IgE Abs. In contrast, the CLA- resting memory T cell population may exert immunoprotective properties toward allergen by high IFN-gamma secretion and induction of IgG4.