Biomedical subjects

H Kohrogi

Publications and source records attributed to H Kohrogi.

At least 19 recordsLinked to original sources

PubMed2006

Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-beta-induced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506. The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated. FK506 inhibited TGF-beta-induced collagen synthesis, and suppressed the expression of TGF-beta type I receptor (TbetaR-I) in TIG-3-20 cells. Consistent with the in vitro findings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part, via reduced TbetaR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival. In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury.

Animals↗

PubMed2001

The role of substance P release in the lung with esophageal acid.

To investigate whether tachykinins are released in the airways by stimulating the esophagus, airway plasma extravasation induced by intraesophageal hydrochloric acid (HCl) in the presence or absence of the neutral endopeptidase (NEP) inhibitor phosphoramidon and the neurokinin-1-receptor antagonist FK888 was studied in anesthetized guinea pigs. Airway plasma extravasation also was studied in the presence of the NEP inhibitor in guinea pigs pretreated with capsaicin or bilateral vagotomy. Propranolol and atropine were used in all animals to block adrenergic and cholinergic nerve effects. Airway plasma leakage was evaluated by measuring extravasated Evans blue dye. One normal HCl infusion into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation induced by HCl infusion into the esophagus in the trachea and main bronchi, and FK888 significantly inhibited extravasation in a dose-related manner. In capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilaterally vagotomized animals. These results suggest that locally acting substances are released by intraesophageal HCl stimulation that cause airway plasma extravasation. These substances are generated through activation of neural pathways, including some that traffic through the vagus nerves that link the esophagus or airways.

Animals↗

PubMed2001

Dyspnoea and hyperventilation induced by synthetic progesterone chlorpromadinone acetate for the treatment of prostatic hypertrophy.

We describe a 74-year-old patient with dyspnoea and tachypnoea induced by chlorpromadinone acetate, a synthetic progesterone used to treat prostatic hyperplasia. The dyspnoea, tachypnoea and hypocapnia improved after discontinuing the chlorpromadinone acetate. It is important to recognize that synthetic progesterones can cause dyspnoea and hyperventilation.

Acetates↗

PubMed2001

Apoptotic response of eosinophils in chronic eosinophilic pneumonia.

To clarify the pathogenesis of chronic eosinophilic pneumonia (CEP), the apoptosis of eosinophils from bronchoalveolar lavage (BAL-Eos) was compared with that of eosinophils from peripheral blood (PB-Eos) in six cases of CEP. The survival rate of eosinophils and the percentage of apoptotic cells of both types of eosinophils were examined, and the effects of interleukin 5 (IL-5) were evaluated. The role of Fas expression in apoptosis of these eosinophils was also studied. The survival rate of BAL-Eos on the third day of culture was significantly higher than that of PB-Eos (p < 0.01). This was associated with a lower proportion of apoptotic cells in BAL-Eos than in PB-Eos; the percentages of apoptotic cells in PB-Eos and BAL-Eos after 24 h of incubation were 21.7 +/- 3.4% and 10.6 +/- 1.7% respectively. IL-5 suppressed apoptosis and increased the survival rate of both PB-Eos and BAL-Eos. It was found that the apoptotic character of BAL-Eos differed from that of PB-Eos in at least three ways. Firstly, the positive rate of Fas expression on PB-Eos was increased after 24 h of incubation, whereas that on BAL-Eos did not change. Secondly, the expression of Fas on PB-Eos was suppressed by IL-5 (18.5 +/- 4.2% - 8.3 +/- 3.2%, p < 0.05), whereas IL-5 failed to suppress Fas expression on BAL-Eos (3.3 +/- 1.6% - 3.6 +/- 1.0%). Lastly, binding of antibody to Fas antigen induced apoptosis of PB-Eos, but not of BAL-Eos. These data suggested that Fas seemed to be involved in the apoptosis of PB-Eos, whereas BAL-Eos were Fas-resistant in chronic eosinophilic pneumonia. In conclusion, apoptosis of eosinophils might be suppressed by proinflammatory cytokines such as IL-5 leading to their accumulation in the lung. Chronic stimulation of eosinophils in the alveolar space with IL-5 may play a crucial role chronic eosinophilic disorders.

Adult↗

PubMed2001

[Lack of knowledge about smoking-related risks for diseases in the general public in Japan].

Cigarette smoking is the primary preventable cause of various diseases and death. Smoking has been causally related to lung cancer, other malignancies, atherosclerosis, coronary heart disease, and chronic obstructive pulmonary disease. There have been few studies, however, of whether the ordinary citizen in Japan understand the risks of serious diseases caused by smoking. Four hundred and thirty six people attended a seminar of respiratory diseases entitled "Cigarette smoking and lung cancer; prevention and treatment of asthma; senile care and prevention of pneumonia". After the seminar, unsigned questionnaires were filled out by 403 of those in attendance. Three hundred eighty nine (165 males and 224 females) respondents correctly answered the questionnaires, and these were analyzed in the study. Attendants comprised 243 who had never smoked (63%), 99 former smokers (25%), and 39 current smokers (10%). Three hundred forty seven attendants (89%) answered that smoking is harmful to the health, and 371 (95%) that it is causally related to lung cancer. In contrast, lower numbers of attendants answered that smoking is causally related to other diseases: pulmonary emphysema, 65% of the responses; chronic bronchitis, 68%; laryngeal cancer, 77%; myocardial infarction, 53%; and atherosclerosis, 49%. Of the 39 current smokers, 27 answered that they would stop smoking after the seminar. Although many people partly understand the risks of smoking, they do not have a clear knowledge of the risks of diseases besides lung cancer. Education about the risks of smoking and about smoking cessation is required.

Adult↗

PubMed2001

[Prevalence of asthma in adults in Menda town rural-mountain area in Japan].

Several reports have suggested that the prevalence of asthma in adults is currently increasing. However, recent prevalence of asthma has not reported in Japan, especially in rural-mountain areas. To investigate the prevalence of asthma in adults in Japan, we conducted clinical epidemiological research on 5066 inhabitants of Menda town, in a rural-mountain area of Japan. The study population comprised 98.7% of adults in the town, including senior high school students whose age were more than 15 years old. The prevalence of asthma among adults was 3.6%. The ratio of prevalence in males to prevalence in females was 1.44. Peaks prevalences were observed in the age ranges of 15-19 and > 70 years old in males, and 15-19, 40-49 and > 70 years old in females.

Adolescent↗

PubMed2000

Isolation of a lactose-binding protein with monocyte/macrophage chemotactic activity. Biological and physicochemical characteristics.

BACKGROUND: We established a T cell line, STO-5, which constitutively produced monocyte/macrophage chemotactic activity via human T cell lymphoma-leukemia-virus-induced transformation of normal human T cells. METHODS: We isolated and purified a lactose-binding protein, MCF-pl5-L (MW of about 50 kD, pl of about 5) from a conditioned medium of STO-5. By using highly purified MCF-pl5-L, its biological and physicochemical properties were elucidated in comparison with C5a and MCP-1. RESULTS: MCF-pl5-L exhibited an evident dose-dependent monocyte chemotactic activity (MCA). MCF-pl5-L had no or little affinity for heparin unlike chemokines such as MCP-1. We further found that MCF-pl5-L exhibited potent chemotactic activity not only for monocytes but also for alveolar macrophages. In contrast, C5a and MCP-1 failed to show evident chemotactic activity for alveolar macrophages though they did show MCA. MCF-pl5-L failed to exhibit evident eosinophil and neutrophil chemotactic activities, indicating its chemotactic activity is selective for monocytes/macrophages. Regarding the biological functions of MCF-pl5-L other than MCA and chemotactic activity for alveolar macrophages, we found that MCF-pl5-L but not C5a and MCP-1 could prolong the life span of alveolar macrophages, probably by inhibiting apoptosis of macrophages, and stimulate the production of TNF-alpha from macrophages. CONCLUSIONS: These results suggest that MCF-pl5-L plays a role as an immune modulator for monocytes/macrophages in the site.

Carrier Proteins↗

PubMed2000

Human bronchial intraepithelial T lymphocytes as a distinct T-cell subset: their long-term survival in SCID-Hu chimeras.

Intestinal intraepithelial T lymphocytes (i-IELs) show features different from those of conventional T cells and play specific roles in the mucosal immunity. To investigate whether human bronchial intraepithelial T lymphocytes (IELs) are a distinct entity, we examined T cells in human bronchial xenografts transplanted on mice with severe combined immune deficiency (SCID). We transplanted human bronchi subcutaneously into mice with SCID, resected the xenografts after various incubation periods (7-174 d), and examined them for CD3(+), CD4(+), CD8(+), and CD45(+) cells by immunohistochemistry. The number of CD3(+) cells in the lamina propria decreased significantly in the first month (from 308.7 +/- 60.2 to 70.9 +/- 49. 4/mm(2); P < 0.05), and xenografts more than 5 mo of age had scant T cells in the lamina propria (5.2 +/- 2.0/mm(2)). However, there was no significant difference between the number of CD3(+) IELs in freshly isolated bronchi and in xenografts maintained for more than 5 mo. In freshly isolated bronchi, the number of CD4(+) IELs was significantly lower than that of CD8(+) cells (2.35 +/- 0.62 versus 4.56 +/- 1.32/mm basement membrane; P < 0.01). After transplantation, the mean CD4-to-CD8 ratio of all xenografts was significantly higher than that of freshly isolated bronchi (5.2 +/- 0.9 versus 0.6 +/- 0.2; P < 0.005). The IELs were positive for CD45, which is specific for human leukocytes, and they were eliminated by irradiation before the transplantation. Almost all IELs (99.5%) in the xenografts expressed alphabeta T-cell receptor, and 35.8% of IELs expressed alpha(e)beta7 integrin. Bronchial epithelial cells in the xenografts expressed interleukin (IL)-7, stem cell factor, intercellular adhesion molecule (ICAM)-1, and human leukocyte antigen-DR (HLA-DR). We conclude that in the SCID-Hu chimera model, human bronchial IELs survive for more than 5 mo, unlike the T cells in the lamina propria, and we suggest that human bronchial IELs may be stimulated by bronchial epithelial cells expressing IL-7, stem cell factor, ICAM-1, and HLA-DR.

Animals↗

PubMed1999

The role of cysteinyl leukotrienes in the pathogenesis of asthma: clinical study of leukotriene antagonist pranlukast for 1 year in moderate and severe asthma.

Clinical studies have shown that pranlukast (Ono Pharmaceutical Co., Osaka, Japan) is effective for mild and moderate asthma. However, it is not well known that pranlukast is also effective on moderate and severe persistent asthma in the long term. We studied the effect of pranlukast on moderate and severe asthmatics by evaluating the change of peak expiratory flow (PEF) and therapeutic scores for 1 year before and during pranlukast therapy. We gave pranlukast 225 mg twice daily orally to 25 patients who were receiving more than 400 micrograms/day beclomethasone inhalation and beta 2 stimulant inhalation with or without oral corticosteroid. Pranlukast increased PEF more than 10 L/min in 14 patients in the first 4 weeks. In these 14 patients, 10 patients continued to monitor PEF and kept asthma diaries for 1 year. We compared the data for 1 year before and during the pranlukast therapy. During the pranlukast therapy, PEF significantly increased, puffs of beta 2 stimulant inhalation significantly decreased. The incidence of oral corticosteroid rescue therapy reduced, and the mean daily dose of oral corticosteroid decreased; however, they were not statistically significant. During treatment with pranlukast, no side effect was observed. From these results, we suggest that pranlukast is effective for more than half of the moderate and severe persistent asthmatics, and that the effectiveness continues for more than 1 year.

Adult↗

PubMed1999

A new look at hypersensitivity pneumonitis.

Hypersensitivity pneumonitis is an immunologically induced lung disease. Although both immune complex-mediated immune response and T cell-mediated immune response are involved in the pathogenesis of the disease, recent studies show the latter mechanism to be more important. As for T cell-mediated immune response, Th1/Th2 and Tc1/Tc2 cytokines produced by CD4+ and CD8+ T cells play important roles in the development of granulomatous inflammation in the lung, a pathologically characteristic feature of the disease. The critical distinction between CD4+ and CD8+ T cells pertains to recognition of antigens presented by different major histocompatibility complex molecules. Serum levels of KL-6 and soluble intercellular adhesion molecule-1 in patients with HP are useful markers of the disease activity. The chronic form of HP can be difficult to diagnose, and provocation testing is helpful. Erythromycin might be useful for anti-inflammatory therapy.

Alveolitis, Extrinsic Allergic↗

PubMed1999

Difference in apoptotic function between eosinophils from peripheral blood and bronchoalveolar lavage in chronic eosinophilic pneumonia.

We compared apoptosis in eosinophils from bronchoalveolar lavage (BAL-Eos) with that in eosinophils from peripheral blood (PB-Eos) of 4 patients with chronic eosinophilic pneumonia (CEP). The survival rate of the BAL-Eos on the 3rd day of the culture was significantly higher than that of the PB-Eos (39.1 vs. 1.3%). The percentage of apoptotic cells in the PB-Eos after a 24-hour incubation was higher than that in the BAL-Eos (21.7 vs. 10.6%) according to an analysis with annexin V. We further found that ECF-PI9, an eosinophil chemotactic factor (ECF) derived from an established T cell line (STO-2), significantly suppressed the apoptosis of both PB-Eos and BAL-Eos and prolonged their survival. The expression of Fas on PB-Eos was significantly suppressed by ECF-PI9 (18.5 to 7.37%, p < 0. 05), whereas ECF-PI9 failed to suppress the Fas expression on BAL-Eos (3.3 to 3.6%). In addition, an ECF with similar physicochemical properties and biological functions was isolated from the BAL fluid of patients with CEP. These data demonstrate differences between PB-Eos and BAL-Eos, and indicate that ECF-PI9 is involved in the pathogenesis of CEP.

Apoptosis↗

PubMed1998

Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines.

To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as may occur in asthma, we examined whether allergic exposure induces the expression of cell adhesion molecules (CAMs) on the bronchial endothelium of passively sensitized human bronchi. Human bronchial tissue obtained from patients undergoing lung cancer surgery was passively sensitized with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 min in the presence or absence of the dust mite allergen. The tissues were stained immunohistochemically for intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1). ICAM-1 was constitutively expressed in both the epithelium and endothelium in all tissues but after allergen stimulation significantly increased at 240 and 480 min. E-selectin expression also existed constitutively and increased significantly at 120 and 240 min with allergen exposure. The constitutive expression of VCAM-1 was less than that of ICAM-1 and E-selectin. Following allergen exposure, VCAM-1 expression increased significantly at 30, 120, 240, and 480 min, and at 480 min reached an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased at 120 min after allergen stimulation, and the interleukin (IL)-1beta level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-alpha, IL-1beta, and IL-4 on human bronchial tissue. TNF-alpha and IL-1beta increased the expression of ICAM-1, E-selectin, and VCAM-1, whereas IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1beta partially blocked the upregulation of CAMs on passively sensitized bronchial tissue after allergen exposure. Thus, both an IgE-dependent allergic response and selected cytokines are able to upregulate endothelial CAMs in human bronchial tissue. These observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.

Adult↗

PubMed1998

Novel phosphodiesterase 4 inhibitor T-440 reverses and prevents human bronchial contraction induced by allergen.

To study the roles of phosphodiesterase (PDE) 4 in the human airways, we examined the effect of the novel PDE4 inhibitor T-440 in the isolated human bronchus. T-440 inhibited PDE4 extracted from human bronchial smooth muscle. IC50 values for the effect of T-440, rolipram (a PDE4 inhibitor) and theophylline on PDE4 activity of the bronchial tissues were 0.08 microM, 2 microM and > 100 microM, respectively. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-5) M histamine-induced contraction, the efficacy of 10(-6) M T-440 being almost the same as that of 3.3 x 10(-5) M aminophylline. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-4) M ACh-induced contraction. But their reversal effects on the ACh-induced contraction were weaker than those on the histamine-induced contraction. T-440 (10(-5) M) significantly reversed the contraction induced by allergen in passively sensitized bronchi. The efficacy of the reversal effect of T-440 (10(-5) M) was significantly higher than that of aminophylline (10(-5) M). T-440 and aminophylline significantly relaxed the basal tension, but pretreatment with T-440 or aminophylline did not significantly prevent histamine- or ACh-induced contraction. In contrast, both T-440 (10(-5) M) and aminophylline (3.3 x 10(-5) M) prevented the contraction induced by allergen, which suggests that PDE4 inhibitor inhibits the release of chemical mediators probably from bronchial mast cells in the allergic response. T-440 (10(-6) M to 10(-5) M) caused the accumulation of cAMP at the concentration that relaxed histamine-induced contraction. Thus selective PDE4 inhibitor is a candidate for the treatment of asthma.

Acetylcholine↗

PubMed1997

Emergency extracorporeal life support for patients with near-fatal status asthmaticus.

Extracorporeal life support (ECLS) was used to treat three patients with near-fatal status asthmaticus who did not respond to aggressive medical therapies and mechanical ventilation under controlled permissive hypercapnia. ECLS was instituted in patient 1 because PaCO2 was excessively high and pH was excessively low, in patient 2 because hypoxemia and shock were not responsive to treatment, and in patient 3 because of sustained severe hypotension. ECLS supported adequate gas exchange until pulmonary function improved, diminishing the need for mechanical ventilation and preventing pulmonary complications. Pulmonary dysfunction improved markedly after only 21 to 86 hours of ECLS. Aggressive medical treatments were continued during ECLS. Our findings indicate that ECLS is a useful method for preventing death in patients with near-fatal status asthmaticus.

Adolescent↗

PubMed1997

Tachykinin antagonist FK224 inhibits neurokinin A-, substance P- and capsaicin-induced human bronchial contraction.

To determine the roles of endogenously released tachykinins (substance P [SP] and neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP, NKA and capsaicin in an organ bath. FK224 (10(-6) M and 10(-5) M, respectively) significantly inhibited NKA-induced contraction and 10(-5) M FK224 shifted the dose-response curve to more than one log unit higher concentration. Because SP- and capsaicin-induced contractions were small, we pretreated the tissues with the neutral endopeptidase inhibitor phosphoramidon (10(-5) M), which inhibits degradation of exogenous tachykinins in order to potentiate the contractions. FK224 (10(-5) M) significantly inhibited SP-induced contraction and it shifted the dose-response curves to about one log unit higher concentration. FK224 (10(-5) M) also significantly inhibited capsaicin-induced contraction and it shifted the dose-response curves to more than one log unit higher concentration. In contrast, FK224 (10(-5) M) did not affect on acetylcholine-, histamine-, and leukotriene D4-induced contraction. These results suggest that FK224 is a tachykinin receptor antagonist in the human bronchial smooth muscle, and that capsaicin-induced contraction is due to endogenously released tachykinin-like substances in the human bronchus.

Acetylcholine↗

PubMed1997

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs.

To investigate whether tachykinins are released in the airways in response to stimulation of the esophagus, we studied the airway plasma extravasation induced by intraesophageal HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-receptor antagonist FK-888 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Infusion of 1 N HCl into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation in the trachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that 1) tachykinin-like substances are released to cause plasma extravasation in the airways as a result of intraesophageal HCl stimulation and 2) there are neural pathways communicating between the esophagus and airways, including the vagus nerve.

Animals↗

PubMed1997

Evidence that allergen-induced contraction of guinea pig bronchi is mediated in part by the release of tachykinins.

To study the role of tachykinins in allergic responses in the airways of guinea pigs sensitized to ovalbumin (OVA), we examined the bronchial contractile response to allergen in the presence or absence of the tachykinin antagonist FK224 in vitro. Because neutral endopeptidase (NEP) effectively cleaves tachykinins, we incubated bronchial tissues with the NEP inhibitor phosphoramidon (10(-5) M) to maintain the activity of endogenously released tachykinins. Then we added 10(-5)% (10 microns/ml) OVA in the presence or absence of FK224 (10(-5) M). FK224 significantly inhibited OVA-induced contraction plateaued and began to relax, we added 10(-5) M phosphoramidon. In the tissue without FK224, phosphoramidon blocked the relaxation and enhanced the contraction. In contrast, in the tissues treated with FK224, phosphoramidon did not enhance the OVA-induced contraction. The enhancement of the contraction induced by phosphoramidon was not inhibited by the sodium channel blocker tetrodotoxin. These results suggest that (1) allergic response causes release of tachykinin-like substances to induce bronchial contraction in part, (2) these responses are blocked by tachykinin antagonist FK224 and (3) nerve conduction is not necessary for the release of tachykinin-like substances induced by allergic response in the guinea pig bronchus.

Allergens↗

PubMed1997

Dermatophagoides farinae-1-derived peptides and HLA molecules recognized by T cells from atopic individuals.

Der f 1, the group I allergen in Dermatophagoides farinae extracts, is a major source of inhalation allergens in Japan. Using the mixture of a panel of overlapping synthetic peptides that spread over the entire Der f 1 molecule, we found that polyclonal Der f 1-specific short-term T cell lines prepared from peripheral blood of 6 individuals allergic to Der f who carry most of the common HLA haplotypes seen in the Japanese population can respond to 16 different peptides. Eight of 16 peptides stimulated T cells of more than 2 donors, regardless of the HLA types. Proliferative responses of four T cell lines were markedly inhibited by mAb HU4 (anti-HLA-DRB1+B5), one was inhibited partially by HU11 (anti-HLA-DQ4+5+6), and one was inhibited fully by a combination of HU4, L243 (anti-HLA-DRB1+B4) and PLM16 (anti-HLA-DRB3) but only partially by each of these mAbs. One of these T cell lines, DT, of which the proliferative response was partially inhibited by HU11, was cloned. Indeed, the T cell clones were restricted by DQ6 molecules on an HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype. These results indicate that patients' T cells recognize Der f 1 in association mainly with HLA-DRA/DRB1, but that DQAI/DQB1, DRA/DRB3 and possibly DRA/DRB4 gene products also function as antigen-presenting molecules. Thus, although some peptides have a more potent T cell-stimulatory activity than others, the T cell receptor ligands formed with the Der f 1 molecule are highly heterogeneous.

Allergens↗