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Biomedical subjects

André-Bernard Tonnel

Publications and source records attributed to André-Bernard Tonnel.

At least 19 recordsLinked to original sources
PubMed2006

Impact of bronchial epithelium on dendritic cell migration and function: modulation by the bacterial motif KpOmpA.

Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c(+) and I-A(d+) myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.

Administration, Intranasal↗
PubMed2006

Diesel exhaust exposure favors TH2 cell recruitment in nonatopic subjects by differentially regulating chemokine production.

BACKGROUND: The prevalence of allergic diseases has increased in the last 20 years, and a number of studies have shown that diesel exhaust particle-associated polyaromatic hydrocarbons can exacerbate the allergic reaction. Much less is known about their potential capacity to generate a T(H)2-type allergic reaction in nonatopic subjects. OBJECTIVE: The aim of this study was to test the hypothesis that diesel exhaust exposure might favor, in nonatopic donors, T(H)2-type cell recruitment, either through increased production of T(H)2-attracting chemokines or decreased production of T(H)1-attracting chemokines. METHODS: PBMCs from nonatopic donors were incubated with diesel exhaust particle-polyaromatic hydrocarbons, and the supernatants were evaluated for the presence of pro-T(H)1 chemokines (IFN-gamma-induced protein 10 and monokine Induced by IFN-gamma) and pro-T(H)2 chemokines (macrophage-derived chemokine, I-309, and pulmonary and activation-regulated chemokine) by means of ELISA. The functional effect was evaluated by using chemotaxis assays with polarized T(H)1 and T(H)2 cells. RESULTS: Diesel exhaust exposure of PBMCs from nonatopic donors induced a late increase after 48 hours in pulmonary and activation-regulated chemokine mediated by IL-13 and a decrease in IFN-gamma-induced protein 10 levels selectively at both the protein and mRNA levels. The functional effect of these chemokine variations resulted in an enhanced chemotaxis of T(H)2, but not T(H)1, cells. CONCLUSION: These findings show that diesel exhaust exposure might be involved in the genesis of allergic diseases by differentially regulating chemokines favoring the recruitment of T(H)2 cells in nonatopic subjects. CLINICAL IMPLICATIONS: Environmental factors, especially air pollution, might favor the genesis of allergic diseases.

Adult↗
PubMed2006

CCR5 usage by CCL5 induces a selective leukocyte recruitment in human skin xenografts in vivo.

CCR5 is one of the major inflammatory chemokine receptors with potential therapeutical applications in humans. However, the redundancy of chemokines and their receptors, and the species specificity of chemokine receptor antagonists pose challenges to understanding of the role they play in pharmacological situations. To address this question, we used a humanized severe combined immunodeficient mouse model grafted with human skin and autologous leukocytes, and evaluated the effect of a blocking antibody against human CCR5, on CCL5-induced cutaneous leukocyte recruitment in vivo. At baseline, CCL5 induced a significant recruitment of T cells mainly of the memory phenotype, of monocytes/macrophages, eosinophils, and IFN-gamma(+) but not IL-4(+) and IL-5(+) cells. In vivo, anti-CCR5 antibody was able to almost completely inhibit the recruitment of monocytes/macrophages and T-helper (Th)1-type cells to inhibit partially the attraction of memory T cells, but had no effect on eosinophil infiltration, although all these cell types express other CCL5 binding chemokine receptors than CCR5. These results indicate that the in vivo environment regulates target cell specificity of CCL5 leading to differential cell recruitment, suggesting that antagonizing CCR5 receptor may be of therapeutic value in diseases such as acquired immuno deficiency syndrome, where CCL5/CCR5, monocytes, and Th1-type cells play a predominant role.

Animals↗
PubMed2006

Involvement of CCL18 in allergic asthma.

Allergic asthma is associated with a pulmonary recruitment of Th type 2 cells, basophils, and eosinophils, mainly linked to chemokine production. CCL18 is a chemokine preferentially expressed in the lung, secreted by APCs, induced by Th2-type cytokines, and only present in humans. Therefore, CCL18 may be involved in allergic asthma. PBMC from asthmatics allergic to house dust mite cultured in the presence of Dermatophagoides pteronyssinus 1 (Der p 1) allergen secreted CCL18, 48 and 72 h after stimulation, whereas those from healthy donors did not. Part of CCL18 was directly derived from Der p 1-stimulated plasmacytoid dendritic cells, whereas the other part was linked to monocyte activation by IL-4 and IL-13 produced by Der p 1-stimulated T cells. In bronchoalveolar lavages from untreated asthmatic allergic patients, CCL18 was highly increased compared with controls. Functionally, CCL18 preferentially attracted in vitro-polarized Th2 cells and basophils, but not eosinophils and Th1 cells, and induced basophil histamine and intracellular calcium release. These data show a new function for CCL18, i.e., the recruitment of Th2 cells and basophils, and suggest that CCL18 may play a predominant role in allergic asthma.

Allergens↗
PubMed2006

Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors.

BACKGROUND: Diagnosis of pulmonary embolism (PE) is difficult in patients with chronic obstructive pulmonary disease (COPD) and exacerbation. OBJECTIVE: To evaluate PE in patients with COPD and exacerbation of unknown origin and explore factors associated with PE. DESIGN: Prospective cohort study. SETTING: University-affiliated hospital in France. PATIENTS: 211 consecutive patients, all current or former smokers with COPD, who were admitted to the hospital for severe exacerbation of unknown origin and did not require invasive mechanical ventilation. MEASUREMENTS: Spiral computed tomography angiography (CTA) and ultrasonography within 48 hours of admission and assessment of the Geneva score. Patients were classified as PE positive (positive results on CTA or negative results on CTA and positive results on ultrasonography) or PE negative (negative results on CTA and negative results on ultrasonography or negative results on CTA and no recurrence of PE at follow-up 3 months later). RESULTS: 49 of 197 patients (25% [95% CI, 19% to 32%]) met the diagnostic criteria for PE. Clinical factors associated with PE were previous thromboembolic disease (risk ratio, 2.43 [CI, 1.49 to 3.94]), malignant disease (risk ratio, 1.82 [CI, 1.13 to 2.92]), and decrease in PaCO2 of at least 5 mm Hg (risk ratio, 2.10 [CI, 1.23 to 3.58]). A total of 9.2% (CI, 4.7% to 15.9%) of patients with a low-probability Geneva score received a diagnosis of PE. An exploratory analysis suggested that substituting malignant disease for recent surgery in the Geneva score might improve its performance in excluding PE in this sample who were more likely to have malignant disease than to have had recent surgery. However, this improvement seems insufficient to exclude PE with enough certainty to withhold therapy for low-risk patients on the basis of the modified score. LIMITATIONS: This study was done in only 1 center. Patients with COPD requiring invasive mechanical ventilation in the intensive care unit were not included. The upper bound of the 95% CI for the low probability of PE according to the Geneva score is too high to rule out PE. The classification of COPD exacerbation of unknown origin was based on the clinician's assessment, not on a standard evaluation for all patients. CONCLUSION: This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin. Three clinical factors are associated with the increased risk for PE. The Geneva score and the modified Geneva score should be prospectively evaluated in patients with COPD.

Aged↗
PubMed2006

Mycobacterium bovis BCG mycobacteria--new application.

The polarized response of T helper-2 (Th2) lymphocytes to an allergen is considered to be the main cause of the pathogenesis of asthma. In this study, we asked a question whether M. bovis BCG mycobacteria which are known for the preferential stimulation of T helper-1 (Th1) immunity, diminish the effector functions of Th2 cells from allergic patients upon stimulation with a common house dust mite Der p-1 allergen. Our results allow a positive answer to this question. We demonstrate that BCG modulates the dendritic cell-dependent allergen presentation process and switches naive T lymphocytes towards an anti-allergic Th1 profile.

Animals↗
PubMed2005

Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response.

The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced during inflammatory reactions, is involved in the control of immune responses, its effect on the differentiation and functions of human monocyte-derived dendritic cells (MDDC) was studied. We show that DC differentiated in the presence of PGD(2) (PG/DC) have an unusual phenotype, with modifications in the expression of molecules involved in antigen (Ag) capture and presentation, leading to higher endocytic and Ag-processing activities. However, under conditions that necessitated Ag processing and presentation, PG/DC have an impaired ability to stimulate naive T cells, whereas superAg-pulsed DC efficiently promote their proliferation. Upon lipopolysaccharide or TNF-alpha/IL-1beta stimulation, PG/DC phenotypically mature but produce abnormal amounts of immunoregulatory cytokines (decreased IL-12p70/IL-10 ratio). Moreover, mature PG/DC fail to up-regulate the chemokine receptor CCR7 and show an impaired migration towards its ligand CCL19. Finally, PG/DC favor the differentiation of naive T cells toward Th2 cells, an effect dependent on IL-10 and inducible costimulator ligand expression by DC. Most of the herein described effects of PGD(2) on MDDC can be reproduced, usually with a higher efficacy, with a selective D prostanoid receptor (DP)1, but not DP2, agonist. Taken as a whole, these results demonstrate that PGD(2) impacts DC differentiation and functions, and extend the concept that it exerts important roles in immunity.

Antigen Presentation↗
PubMed2005

Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment.

BACKGROUND: Airway dendritic cells (DCs) are crucial for allergen-induced sensitization and inflammation in allergic asthma. After allergen challenge, an increased number of DCs is observed in airway epithelium from patients with allergy. OBJECTIVE: Because Der p 1, a cysteine protease allergen from Dermatophagoides pteronyssinus , induces chemokine production by bronchial epithelial cells (BECs), the purpose of this investigation was to evaluate the capacity of BEC exposed to Der p 1 to recruit DCs. METHODS: Chemotactic activity of BEAS-2B, a bronchial epithelial cell line, and BECs from nonatopic controls and patients with allergic asthma was evaluated on the migration of precursors, immature and mature monocyte-derived DCs (MDDCs), and CD34 + -derived Langerhans cells (LCs). RESULTS: C-C chemokine ligand (CCL)-2, CCL5, and C-X-C chemokine ligand 10 production by BEAS-2B and BEC was increased after Der p 1 exposure, whereas the proenzyme proDer p 1 devoid of enzymatic activity had no effect. Der p 1 stimulation of BEAS-2B and BEC from both groups increased significantly the recruitment of MDDC precursors, depending on CCL2, CCL5, and C-X-C chemokine ligand 10 production. In a reconstituted polarized epithelium, apical application of Der p 1 enhanced MDDC precursor migration into the epithelial layer. Moreover, Der p 1 stimulation of BEC from patients with asthma but not from controls increased the migration of LC precursors, mainly dependent on CCL20 secretion. No migration of immature and mature DCs was observed. CONCLUSION: These data confirmed that BECs participate in the homeostasis of the DC network present within the bronchial epithelium through the secretion of chemokines. In allergic asthma, upregulation of CCL20 production induced LC recruitment, the role of which remains to be determined.

Adult↗
PubMed2005

Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed dendritic cells from allergic patients.

BACKGROUND: Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. OBJECTIVE: The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. METHODS: MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. RESULTS: LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1-pulsed DCs. CONCLUSION: Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.

Animals↗
PubMed2005

[Specific immunotherapy and therapeutic strategies in allergic diseases. What's new?].

Specific immunotherapy (SIT) can induce tolerance of airborne allergens in patients with rhinitis, conjunctivitis and asthma. SIT is also effective for venom anaphylaxis. In contrast, SIT is not recommended in severe asthma, food allergy or skin allergy. The mechanisms of SITare unclear, but attention has recently focused on regulatory T cells and their capacity to induce tolerance via IL10 and TGF-alfa production. Recent studies show that SIT not only reduces symptom scores but also modifies the natural history of allergic diseases, preventing sensitization to new allergens and/or limiting the onset of asthma in children with rhinitis. Another recent advance is sublingual IT which is allergic effective and suppresses the risk of systemic anaphylactic reactions. Alternatives to SIT are in the pipeline, such as recombinant allergens, nude DNA vaccines, and immunostimulatory sequence/allergen complexes.

Adjuvants, Immunologic↗
PubMed2004

Migration and accumulation of eosinophils toward regional lymph nodes after airway allergen challenge.

BACKGROUND: Eosinophils play a major role in allergic airway inflammation because of their ability to release toxic mediators. In addition, they are able to migrate toward draining thoracic lymph nodes (TLNs) after intratracheal administration, where they can function as antigen-presenting cells. OBJECTIVE: In this study, we evaluated in vivo eosinophil migration toward the TLN after allergen sensitization and analyzed expression of molecules involved in antigen presentation. METHODS: Mice were sensitized by intraperitoneal injection of ovalbumin on days 1 and 10 and challenged once intranasally with ovalbumin on day 20. The kinetics of eosinophilia was evaluated in blood, lung tissue homogenate, bronchoalveolar lavage fluid, and TLN. Cell surface staining was analyzed by flow cytometry. RESULTS: The kinetics of eosinophil recruitment was similar in TLN, lung tissue, and blood, beginning at 12 hours and peaking at 48 hours after allergen challenge. Approximately 70% of TLN eosinophils expressed MHC class II molecules, compared with less than 25% in blood and lungs. Moreover, TLN eosinophils expressed higher levels of MHC class II and CD86 compared with blood and lung eosinophils. Most eosinophils expressed CD80 and CD54, whereas only a few eosinophils expressed CD40. Eosinophils in lungs and TLN appeared to be activated with lower CD62-ligand expression compared with blood eosinophils. CONCLUSION: The presence of eosinophils with a different phenotype in the TLN at early time points after allergen challenge of sensitized mice supports their capacity to serve as antigen-presenting cells, sustaining allergic/inflammatory responses in the airways.

Administration, Inhalation↗
PubMed2003

Outer membrane protein A from Klebsiella pneumoniae activates bronchial epithelial cells: implication in neutrophil recruitment.

Aside from its mechanical barrier function, bronchial epithelium plays an important role both in the host defense and in the pathogenesis of inflammatory airway disorders. To investigate its role in lung defense, the effect of a bacterial cell wall protein, the outer membrane protein A from Klebsiella pneumoniae (kpOmpA) on bronchial epithelial cells (BEC) was evaluated on adhesion molecule expression and cytokine production. Moreover, the potential implication of this mechanism in kpOmpA-induced lung inflammation was also determined. Our in vitro studies demonstrated that kpOmpA strongly bound to BEAS-2B cells, a human BEC line, and to BEC primary cultures, resulting in NF-kappaB signaling pathway activation. Exposure to kpOmpA increased ICAM-1 mRNA and cell surface expression, as well as the secretion of IL-6, CXC chemokine ligand (CXCL)1, CXCL8, C-C chemokine ligand 2, CXCL10 by BEAS-2B cells, and BEC primary cultures (p < 0.005). We analyzed in vivo the consequences of intratracheal injection of kpOmpA to BALB/c mice. In kpOmpA-treated mice, a transient neutrophilia (with a maximum at 24 h) was observed in bronchoalveolar lavage and lung sections. In vivo kpOmpA priming induced bronchial epithelium activation as evaluated by ICAM-1 and CXCL1 expression, associated with the secretion of CXCL1 and CXCL5 in bronchoalveolar lavage fluids. In the lung, an increased level of the IL-6, CXCL1, CXCL5, CXCL10 mRNA was observed with a maximum at 6 h. These data showed that kpOmpA is involved in host defense mechanism by its ability to activate not only APC but also BEC, resulting in a lung neutrophilia.

Animals↗
PubMed2003

Overexpression of endocan induces tumor formation.

Endocan is a proteoglycan specifically secreted by endothelial cells. Through its glycan domains, endocan binds to hepatocyte growth factor and increases its mitogenic activity. Here, we show that human embryonic kidney 293 cells, which have been genetically engineered to overexpress endocan, form tumors when injected s.c. in SCID mice. Both the glycan and a phenylalanine-rich region of endocan are necessary for mediating tumor growth activity. Blocking the phenylalanine-rich region with a monoclonal antibody results in a marked reduction of tumor growth. Finally, we report that circulating levels of endocan are increased in mice with the endocan-expressing human embryonic kidney 293 cell tumors and in a series of adult patients with lung cancer. Taken together, these results suggest that (a) endothelial-derived endocan induces tumor growth, (b) antibodies to endocan may have therapeutic potential, and (c) circulating levels of endocan may eventually represent a novel marker for cancer.

Animals↗
PubMed2003

Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells.

Among the factors produced at inflammatory sites and those capable of modulating dendritic cell (DC) functions, PGD(2) may be important in the outcome of immune responses. The biological roles for PGD(2) are in part effected through two plasma membrane G protein-coupled receptors: the D prostanoid (DP) receptor and the chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes (CRTH2). In this report, we studied the effects of PGD(2) and of its major physiological metabolite, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), on the functions of human monocyte-derived DC. First, we show that PGD(2) exerts in vitro chemotactic effects on monocytes via CRTH2 activation while it inhibits the chemokine-driven migration of monocyte-derived DC through DP. We also report that PGD(2) and 15d-PGJ(2) alter the LPS- and allergen-induced DC maturation and enhance the CD80/CD86 ratio on mature DC in a DP- and CRTH2-independent manner. Moreover, PGD(2) and 15d-PGJ(2) strongly reduce the secretion of the Th1 promoting cytokine IL-12 and affect the synthesis of chemokines involved in Th1 cell chemotaxis, particularly CXCL10. Inhibition of cytokine/chemokine secretion implicates at least in part DP, but not CRTH2. The effects exerted by PGD(2) are associated with the phosphorylation of CREB, but do not parallel with the deactivation of the NF-kappa B and mitogen-activated protein kinase pathways. In contrast, 15d-PGJ(2) seems to target other cellular proteins. Finally, in a model of Th CD45RA(+) differentiation induced by allergen- and superantigen-pulsed DC, PGD(2) impacts on the orientation of the immune response by favoring a Th2 response.

Cell Differentiation↗
PubMed2003

Effect of diesel on chemokines and chemokine receptors involved in helper T cell type 1/type 2 recruitment in patients with asthma.

The objective of this study was to evaluate if diesel exhausts could favor helper T cell type (Th) 2-associated allergic reactions either through an increased production of Th2-associated chemokines and of their associated receptors or through a decrease of Th1-attracting chemokines and chemokine receptors. Diesel but not allergen exposure of peripheral blood mononuclear cells from subjects with allergy induced a release of I-309, whereas both diesel and Der p 1 induced an early but transient release of monokine induced by IFN-gamma and a late release of pulmonary and activation-regulated chemokine. Although both Th1- and Th2-attracting chemokines were induced, the resulting effect was an increased chemotactic activity on Th2 but not Th1 cells. Surprisingly, diesel induced a late increase in the expression of the Th1-associated CXC receptor 3 and CC receptor 5. T cell CXC receptor 3 upregulation was not associated with an increased migration to its ligands. These two antagonistic effects have been previously reported as a scavenger mechanism to clear chemokines. Altogether, these results suggest that diesel, even without allergen, may amplify a type 2 immune response but that it can also increase late Th1-associated chemokine receptor expression, perhaps as a scavenger mechanism to clear pro-Th1 chemokines and promote the Th2 pathway.

Allergens↗
PubMed2003

Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response.

Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4(+) T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-gamma(high)/IL-4(low)] and Der p 1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T cell polarization (IFN-gamma(low)/IL-4(low)) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.

Animals↗
PubMed2002

Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: involvement of CCR7.

In rodents, airway dendritic cells (DCs) capture inhaled Ag, undergo maturation, and migrate to the draining mediastinal lymph nodes (MLN) to initiate the Ag-specific T cell response. However, the role of human DCs in the pathogenesis of the Th2 cell-mediated disease asthma remains to be clarified. Here, by using SCID mice engrafted with T cells from either house dust mite (HDM)-allergic patients or healthy donors, we show that DCs pulsed with Der p 1, one of the major allergens of HDM, and injected intratracheally into naive animals migrated into the MLN. In the MLN, Der p 1-pulsed DCs from allergic patients induced the proliferation of IL-4-producing CD4(+) T cells, whereas those from healthy donors induced IFN-gamma-secreting cells. In reconstituted human PBMC-reconstituted SCID mice primed with pulsed DCs from allergic patients, repeated exposure to aerosols of HDM induced 1) a strong pulmonary inflammatory reaction rich in T cells and eosinophils, 2) an increase in IL-4 and IL-5 production in the lung lavage fluid, and 3) increased IgE production compared with that in mice primed with unpulsed DCs. All these effects were reduced following in vivo neutralization of the CCR7 ligand secondary lymphoid tissue chemokine. These data in human PBMC-reconstituted SCID mice show that monocyte-derived DCs might play a key role in the pathogenesis of the pulmonary allergic response by inducing Th2 effector function following migration to the MLN.

Aerosols↗