krn-7000 and Asthma

To assess the efficacy of conventional treatment combined with bacterial lysate [OM-85 Broncho-Vaxom (BV)] in the prevention of asthma in children as well as its influence on the number of natural killer T (NKT) cells and their cytokine production.. Sixty children diagnosed with asthma were divided into either a BV-treated group (with oral OM-85 BV) or a conventional inhaled corticosteroid (ICS) group. The numbers of NKT cells and CD4+ NKT cells were measured in the peripheral blood by flow cytometry. The levels of IFN-γ, IL-4, and IL-10 after the blood cells had been cultured with an NKT cell agonist were detected by ELISA.. After therapy, asthma attacks were significantly decreased compared with before therapy in both groups. However, after therapy, respiratory tract infections were reduced compared with before therapy in the BV-treated group only. Additionally, the frequency of asthma attacks and use of antibiotics in the BV-treated group were lower than in the ICS group. With BV treatment, the numbers of peripheral blood NKT cells and CD4+ NKT cells were higher after therapy than before therapy. After therapy, the ratio of IFN-γ/IL-4 and IL-10 levels were increased in the BV-treated group, whereas IL-4 was reduced in the BV-treated group compared with the ICS group.. BV combined with conventional asthma treatment can prevent recurrent respiratory tract infections and suppress the severity of asthma attacks, possibly by altering the rates and cytokines of NKT cells.

Topics: Adjuvants, Immunologic; Adolescent; Asthma; Cell Extracts; Child; Child, Preschool; Female; Galactosylceramides; Humans; Interferon-gamma; Interleukin-10; Interleukin-4; Lymphocyte Count; Male; Natural Killer T-Cells

Although natural killer T cells (NKT cells) are altered in obese asthmatic mice, their function remains completely unclear. To further explore the potential mechanism of NKT cells in airway inflammation of obesity-associated asthma, we examined the effects of α-galactosylceramide (KRN7000) on airway inflammation in obese asthmatic mice. Male C57BL/6J mice were divided into five groups: (1) control; (2) asthma; (3) A + KRN, asthma with KRN7000; (4) obese asthma; and (5) OA + KRN, obese asthma with KRN7000. Cytometric bead array (CBA) was used to detect interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the serum. Flow cytometry was used to detect NKT cells and CD69

Topics: Adjuvants, Immunologic; Animals; Asthma; Diet, High-Fat; Galactosylceramides; Inflammation Mediators; Killer Cells, Natural; Male; Mice; Mice, Inbred C57BL; Obesity; Ovalbumin

Some studies have shown that maturation of dendritic cells (DCs) is modulated directly by pathogen components via pattern recognition receptors such as Toll-like receptors, but also by signal like CD40 ligand (CD40 L or CD154) mediated by activated T cells. Several reports indicate that invariant natural killer T (iNKT) cells up-regulate CD40 L upon stimulation and thereby induce activation and maturation of DCs through crosslink with CD40. Our previous findings indicated that iNKT cells promote Th2 cell responses through the induction of immunogenic maturation of lung DCs (LDCs) in the asthmatic murine, but its mechanism remains unclear. Therefore, we investigated the immunomodulatory effects of blockade of CD40 L using anti-CD40 L treatment on Th2 cell responses and immunogenic maturation of LDCs, and further analyzed whether these influences of blockade of CD40 L were related to lung iNKT cells using iNKT cell-deficient mice and the combination treatment of specific iNKT cell activation with anti-CD40 L treatment in murine models of asthma. Our findings showed that blockade of CD40 L using anti-CD40 L treatment attenuated Th2 cell responses in wild-type (WT) mice, but not in CD1d-deficient mice sensitized and challenged with ovalbumin (OVA) or house dust mite (HDM). Meanwhile, blockade of CD40 L down-regulated immunogenic maturation of LDCs in WT mice, but not in CD1d-deficient mice sensitized and challenged with OVA. Additionally, agonistic anti-CD40 treatment reversed the inhibitory effects of anti-CD40 L treatment on Th2 cell responses and LDC activation in an OVA-induced mouse model of asthma. Furthermore, LDCs from asthmatic mice treated with anti-CD40 L could significantly reduce the influence on Th2 cell responses in vivo and in vitro. Finally, α-Galactosylceramide plus anti-CD40 L treatment stimulated lung iNKT cells, but suppressed Th2 cell responses in the asthmatic mice. Taken together, our data raise an evidence that blockade of CD40 L attenuates Th2 cell responses through the inhibition of immunogenic maturation of LDCs, which may be at least partially related to lung iNKT cells in murine models of asthma.

Topics: Animals; Antigens, CD1d; Asthma; CD40 Ligand; Cell Communication; Dendritic Cells; Disease Models, Animal; Female; Galactosylceramides; Humans; Lung; Mice; Mice, Knockout; Natural Killer T-Cells; Ovalbumin; Pyroglyphidae; Th2 Cells

Asthma is a common inflammatory pulmonary disorder involving a diverse array of immune cells such as proinflammatory T helper 2 (Th2) cells. We recently reported that intraperitoneal injection of α-galactosylceramide (α-GalCer) can stimulate the lung invariant natural killer T (iNKT) cells and does not lead to airway inflammation in WT mice. Other studies indicate that iNKT cells play an important role in inducing regulatory T cells (Treg cells) and peripheral tolerance. Using iNKT cell- knockout mice, functional inactivation of Treg cells, and co-culture experiments in murine asthma models, we investigated the immunoregulatory effects of α-GalCer treatment before allergen sensitization on Th2 cell responses. We also studied whether α-GalCer's effects require lung Treg cells induced by activated iNKT cells. Our results disclosed that intraperitoneal administration of α-GalCer before allergen sensitization could promote the expansion and suppressive activity of lung CD4

Topics: Allergens; Animals; Asthma; Dendritic Cells; Disease Models, Animal; Female; Galactosylceramides; Mice; Mice, Inbred BALB C; Mice, Knockout; Natural Killer T-Cells; Pyroglyphidae; T-Lymphocytes, Regulatory; Th2 Cells

Chronic inflammatory disorder of the airways causes asthma. Regulatory T cells (Treg cells) and Natural killer T cells (NKT cells) both play critical roles in the pathogenesis of asthma. Activation of Treg cells requires Foxp3, whereas whether Foxp3 may regulate the ratio of Treg and NKT cells to affect asthma is uncertain. In an ovalbumin (OVA)-induced mouse model of asthma, we either increased Treg cells by lentivirus-mediated forced expression of exogenous Foxp3, or increased NKT cells by stimulation with its activator α-GalCer. We found that the CD4+CD25+ Treg cells increased by forced Foxp3 expression, and decreased by α-GalCer, while the CD3+CD161+ NKT cells decreased by forced Foxp3 expression, and increased by α-GalCer. Moreover, forced Foxp3 expression, but not α-GalCer, significantly alleviated the hallmarks of asthma. Furthermore, forced Foxp3 increased levels of IL_10 and TGFβ1, and α-GalCer increased levels of IL_4 and INFγ in the OVA-treated lung. Taken together, our study suggests that Foxp3 may activate Treg cells and suppress NKT cells in asthma. Treg and NKT cells may antagonize the effects of each other in asthma.

Topics: Animals; Asthma; Cytokines; Disease Models, Animal; Forkhead Transcription Factors; Galactosylceramides; HEK293 Cells; Humans; Hypersensitivity; Lentivirus; Male; Mice, Inbred C57BL; Natural Killer T-Cells; Ovalbumin; T-Lymphocytes, Regulatory

Invariant natural killer T cells (iNKT cells) are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4+ and CD8+ T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail.. In this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA)-induced murine model of asthma.. Our results demonstrate that α-Galactosylceramide (α-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice. In the OVA-induced asthma model, α-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF); increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice.. These results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma.

Topics: Adoptive Transfer; Animals; Antigens, CD1d; Asthma; Disease Models, Animal; Female; Galactosylceramides; Inflammation; Mice; Mice, Inbred BALB C; Natural Killer T-Cells; Ovalbumin; Th2 Cells

IL-17A is associated with different asthma phenotypes as virus-associated or steroid-resistant asthma. Invariant natural killer T (iNKT) cells play an important role in the pathogenesis of asthma. The aim of the study was to evaluate the activity of polyinosinic-polycytidylic acid [poly(I:C)] on IL-17A production by CD1d-activated iNKT cells.. We analysed the in vitro effect of poly(I:C) on the release of IL-17A by spleen and lung CD1d-activated iNKT cells with α-galactosylceramide (α-GalCer). Its activity was also investigated in an α-GalCer-induced murine models, including lung inflammation. The inhibition of IL-17A by Toll-like receptor (TLR) 7 agonists in the same in vitro and in vivo models has been analysed.. Poly(I:C) upregulated the in vitro IL-17A production by CD1d-activated NK1.1- CD4- iNKT subset, without modifying type 1 and type 2 cytokines. The two stimuli selectively upregulated IL-17A serum levels in vivo. Their intratracheal administration resulted in increased airway hyper-reactivity (AHR), neutrophilia in bronchoalveolar lavage and airway inflammation, which were inhibited by anti-IL-17A antibody. Poly(I:C) effects were attributable to IL1β and IL-23 release from dendritic cells, as showed by inhibition with neutralizing antibodies. TLR7 agonists inhibited the IL-17A production by poly(I:C) plus α-GalCer in the same models. Such effect was associated with the increased production by DC of IL-17A-inhibiting cytokines and the dampening of IL-1β and IL-23.. Synthetic dsRNA selectively expand a CD1d-driven IL-17A-producing iNKT cell subset, thus explaining the worsening of airway inflammation by some viral infections. TLR3- and TLR7-triggering viral sequences can exert variable and opposite effects on adaptive immune response.

Topics: Animals; Antigens, CD1d; Asthma; Bronchoalveolar Lavage Fluid; Galactosylceramides; Humans; Inflammation; Interleukin-17; Mice; Natural Killer T-Cells; Poly I-C

To investigate the effects of specific immunotherapy on the NKT cells in peripheral blood and the ability of NKT cells to proliferate in response to alpha-galactosylceramide (alpha-GalCer) in house-dust-mite- (HDM-) sensitized asthma children, peripheral blood mononuclear cells were isolated from 42 asthmatic children, of whom 24 were on specific immunotherapy (SIT) for more than a year and 20 were healthy. Compared with control group, the ratio of peripheral blood NKT and CD4(+)NKT cells was significantly decreased (P < 0.01) and was elevated in SIT asthma group (P < 0.05), respectively, but it was still less than the normal control group (P < 0.01). The level of IL-4 in serum secreted by NKT cells in asthma group was significantly higher than that of control group (P < 0.01), particularly apparent after 72 hours. The level of IL-4 in SIT group decreased significantly (P < 0.01). The level of IL-10 in serum secreted by NKT cells in asthma group was decreased significantly than that of the control group (P < 0.01) especially in 48 hours, while that of SIT group was increased significantly (P < 0.01). These results suggest that the pathogenesis of asthma may be related to the ratio and dysfunction of NKT and CD4(+)NKT cells.

Topics: Adolescent; Animals; Asthma; Case-Control Studies; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Female; Galactosylceramides; Humans; Immunotherapy; Interleukin-10; Interleukin-4; Leukocytes, Mononuclear; Male; Natural Killer T-Cells; Pyroglyphidae

Invariant NKT (iNKT) cells bridge innate and adaptive immune responses, resulting in the expansion of Ag-specific B and T cell responses. α-Galactosylceramide (α-GalCer), the most studied glycolipid that activates iNKT cells, has been proposed to be an effective adjuvant against infections and tumors. We found that the activation of iNKT cells by intranasal injection of α-GalCer induced airway eosinophilia in naive mice. Eosinophils, which mediate tissue damage and dysfunction by secreting mediators, play important roles in the pathogenesis of allergic diseases. In this study, we investigated the mechanism of how eosinophils are recruited to the lung by α-GalCer. Our results demonstrated that α-GalCer-induced eosinophil inflammation was mediated through iNKT cells. These cells secreted IL-5 to recruit eosinophils directly to the lung and/or secreted IL-4 and IL-13 to recruit eosinophils indirectly by inducing lung epithelial cells, endothelial cells, and fibroblast to secrete the eosinophil chemoattractant eotaxin. In addition, in the OVA-alum murine model of allergic asthma, α-GalCer administration in OVA-immunized mice also increased airway eosinophilia after challenge. Given our findings, intranasal administration of α-GalCer induced airway eosinophilic inflammation in both naive and allergic mice. Hence, it remains to be determined whether the activation of iNKT cells would be applicable in therapeutics for human diseases.

Topics: Administration, Intranasal; Alum Compounds; Animals; Antigens, CD1d; Asthma; Bronchoalveolar Lavage Fluid; Cells, Cultured; Chemokines, CC; Enzyme-Linked Immunosorbent Assay; Eosinophilia; Eosinophils; Female; Galactosylceramides; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Knockout; Natural Killer T-Cells; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction

This study evaluates the ability of a novel TLR7 ligand (9-benzyl-2-butoxy-8-hydroxy adenine, called SA-2) to affect IL-17 response. The SA-2 activity on the expression of IL-17A and IL-17-related molecules was evaluated in acute and chronic models of asthma as well as in in vivo and in vitro α-galactosyl ceramide (α-GalCer)-driven systems. SA-2 prepriming reduced neutrophils in bronchoalveolar lavage fluid and decreased methacoline-induced airway hyperresponsiveness in murine asthma models. These results were associated with the reduction of IL-17A (and type 2 cytokines) as well as of molecules favoring Th17 (and Th2) development in lung tissue. The IL-17A production in response to α-GalCer by spleen mononuclear cells was inhibited in vitro by the presence of SA-2. Reduced IL-17A (as well as IFN-γ and IL-13) serum levels in mice treated with α-GalCer plus SA-2 were also observed. The in vitro results indicated that IL-10 produced by B cells and IL-10-promoting molecules such as IFN-α and IL-27 by dendritic cells are the major player for SA-2-driven IL-17A (and also IFN-γ and IL-13) inhibition. The in vivo experiments with anti-cytokine receptor Abs provided evidence of an early IL-17A inhibition essentially due to IL-10 produced by resident peritoneal cells and of a delayed IL-17A inhibition sustained by IFN-α and IL-27, which in turn drive effector T cells to IL-10 production. These findings suggest that such TLR7 agonist downregulating Th17 (as well as Th2) response has to be considered a valid candidate for novel vaccine formulations in allergy.

Topics: Adenine; Animals; Asthma; B-Lymphocytes; Cells, Cultured; Cytokines; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Female; Galactosylceramides; Gene Expression; Injections, Intraperitoneal; Interferon-gamma; Interleukin-10; Interleukin-13; Interleukin-17; Leukocytes, Mononuclear; Lung; Mice; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; Th17 Cells; Th2 Cells; Toll-Like Receptor 7

Using an allergen-induced airway inflammation model, we show that an injection of alpha-galactosylceramide (alpha-GalCer), a ligand for invariant NK T (iNKT) cells, induced IL-27 and that this process is essential for the attenuation of the Th2 response. After the systemic administration of alpha-GalCer into the mice primed with OVA in alum, Th2 cytokine production of OVA-primed CD4(+) T cells in their lymph nodes, IgG1 and IgE Ab formation, and infiltration of eosinophils in bronchoalveolar lavage after the OVA challenge were suppressed. Systemic administration of rIFN-gamma into OVA-primed mice could not reproduce these effects of alpha-GalCer. IL-27p28 was detected both in the culture supernatant of alpha-GalCer-stimulated spleen cells and in the serum of the alpha-GalCer-treated mice, but not in the iNKT cell-deficient mice. Splenic iNKT cells produced IL-27p28 in the culture supernatant upon stimulation with PMA plus ionomycin, although the transcript of IL-27p28 in the iNKT cells was constitutively expressed regardless of the stimulation. By contrast, the transcript of IL-27EBI3 was induced in the iNKT cells upon stimulation with PMA plus ionomycin in vitro and with alpha-GalCer treatment in vivo, suggesting that IL-27 (p28/EBI3) could be produced by iNKT cells in an activation-dependent manner. Although repeated injections of rIL-27 did not substitute for the effects of a single injection of alpha-GalCer, administration of rIL-27 along with rIFN-gamma reproduced in vivo effects of the alpha-GalCer injection. These data indicate that production of both IL-27 and IFN-gamma by the alpha-GalCer treatment is responsible for suppression of the Th2 response and allergic inflammation.

Topics: Animals; Asthma; Cells, Cultured; Disease Models, Animal; Female; Galactosylceramides; Hypersensitivity; Immunosuppression Therapy; Inflammation Mediators; Injections, Intraperitoneal; Interferon-gamma; Interleukins; Ligands; Mice; Mice, Inbred BALB C; Mice, Knockout; Natural Killer T-Cells; Th2 Cells

IL-33 is an IL-1 family member recently identified as the ligand for T1/ST2 (ST2), a member of the IL-1 receptor family. ST2 is stably expressed on mast cells and T(h)2 effector T cells and its function has been studied in the context of T(h)2-associated inflammation. Indeed, IL-33 induces T(h)2 cytokines from mast cells and polarized mouse T cells and leads to pulmonary and mucosal T(h)2 inflammation when administered in vivo. To better understand how this pathway modulates inflammatory responses, we examined the activity of IL-33 on a variety of human immune cells. Human blood-derived basophils expressed high levels of ST2 receptor and responded to IL-33 by producing several pro-inflammatory cytokines including IL-1 beta, IL-4, IL-5, IL-6, IL-8, IL-13 and granulocyte macrophage colony-stimulating factor. Next, utilizing a human T(h)2-polarized T cell culture system derived from allergic donor blood cells, we found that IL-33 was able to enhance antigen-dependent and -independent T cell responses, including IL-5, IL-13 and IFN-gamma production. IL-33 activity was also tested on V alpha 24-positive human invariant NKT (iNKT) cells. In the presence of alpha-galactosylceramide antigen presentation, IL-33 dose dependently enhanced iNKT production of several cytokines, including both IL-4 and IFN-gamma. IL-33 also directly induced IFN-gamma production from both iNKT and human NK cells via cooperation with IL-12. Taken together, these results indicate that in addition to its activity on human mast cells, IL-33 is capable of activating human basophils, polarized T cells, iNKT and NK cells. Moreover, the nature of the responses elicited by IL-33 suggests that this axis may amplify both T(h)1- and T(h)2-oriented immune responses.

Topics: Antigens, Dermatophagoides; Asthma; Basophils; Cell Culture Techniques; Cytokines; Escherichia coli; Flow Cytometry; Galactosylceramides; Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Killer Cells, Natural; Lymphocyte Activation; Receptors, Cell Surface; Recombinant Proteins; Th2 Cells

alpha-Galactosylceramide (alpha-GalCer) is a specific ligand of natural killer T cells (NKT cells) that regulates the immune responses such as tumor rejection and autoimmunity by producing interferon (IFN)-gamma and interleukin (IL)-4. However, it has not been determined whether alpha-GalCer-activated NKT cells modulate allergic inflammation. Because alpha-GalCer induces a large amount of IFN-gamma production by NKT cells, we hypothesized that an in vivo administration of alpha-GalCer could inhibit allergic airway inflammation in mice. Strikingly, a single intraperitoneal injection of alpha-GalCer almost completely abrogated an infiltrate with eosinophils in the lung tissue as well as in the bronchoalveolar lavage. This inhibition of allergic inflammation was associated with a significant decrease in the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and in the number of goblet cells. In addition, this ligand significantly inhibited airway hyperresponsiveness to inhaled methacholine and raised the serum levels of ovalbumin-specific IgG2a with a decrease in those of ovalbumin-specific IgE. In IFN-gamma knockout mice, however, alpha-GalCer failed to exert such inhibitory effects in this asthma model. These results indicate that alpha-GalCer prevents allergic airway inflammation possibly through IFN-gamma production by ligand-activated NKT cells, suggesting the potential therapeutic application of alpha-GalCer in asthma.

Topics: Animals; Antigens; Asthma; Bronchoalveolar Lavage Fluid; Cytotoxicity, Immunologic; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Galactosylceramides; Goblet Cells; Hyperplasia; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Inflammation; Interferon-gamma; Killer Cells, Natural; Ligands; Lung; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; T-Lymphocytes; Th2 Cells; Time Factors

Allergic asthma is a multifaceted syndrome consisting of eosinophil-rich airway inflammation, bronchospasm, and airway hyper-responsiveness (AHR). Using a mouse model of allergic asthma, we previously reported that invariant NKT (iNKT) cells increase the severity of this disease. Herein, we demonstrate that a single i.v. injection of alpha-galactosylceramide (alpha-GalCer), 1 h before the first airway allergen challenge of OVA-sensitized mice, abrogates elicitation of AHR, airway eosinophilia, IL-4 and IL-5 production in bronchoalveolar lavage fluid, and specific anti-OVA IgE antibodies. Further, alpha-GalCer administered intranasally also strongly inhibited the major symptoms of asthma in sensitized and challenged mice. Alpha-GalCer treatment induces iNKT cell accumulation in the lungs, and shifts their cytokine profile from pro-asthmatic IL-4 to a protective IFN-gamma production. The role of IFN-gamma from iNKT cells in protection was shown by adoptive transfer of sorted iNKT cells from OVA-sensitized and alpha-GalCer-treated mice which protected immunized recipients from manifesting asthma by an IFN-gamma-dependent pathway. Our findings demonstrate for the first time that alpha-GalCer administered locally inhibits asthma symptoms, even in predisposed asthmatic mice, through an iNKT cell- and IFN-gamma-dependent pathway.

Topics: Administration, Intranasal; Adoptive Transfer; Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Flow Cytometry; Galactosylceramides; Hypersensitivity; Injections, Intravenous; Interferon-alpha; Killer Cells, Natural; Male; Mice; Ovalbumin

Recent studies suggest that therapies targeted at depletion or limiting of natural killer (NK) T cells may be a possible strategy for the treatment of asthma. In the present study, we measured the number of circulating V alpha24+ NKT cells in 32 asthmatic patients and compared these patients with 29 nonatopic healthy controls. We investigated the relationships between NKT cell number and clinical variables such as the number of eosinophils, the circulating level of IgE, and the severity of asthma. In addition, we also investigated the ability of NKT cells to proliferate in response to alpha-galactosyl ceramide (alpha-GalCer) in vitro. The V alpha24+ NKT cell counts of asthmatic patients were significantly lower than those of healthy controls. There were no significant differences observed in asthmatic patients among the subgroups in terms of atopic status and severity. There was no significant correlation between the number of NKT cells and clinical variables. The proliferative response to alpha-GalCer of the patients and controls was not significantly different, indicating no intrinsic proliferative defect of NKT cells in asthma. These results suggest that the number of circulating NKT cells was already decreased in patients with asthma. Further study, such as the evaluation of lung NKT cells, will be needed to determine the role of NKT cells in patients with asthma.

Topics: Adult; Aged; Asthma; Cell Proliferation; Eosinophils; Female; Galactosylceramides; Humans; Immunoglobulin E; In Vitro Techniques; Killer Cells, Natural; Leukocyte Count; Male; Middle Aged; Severity of Illness Index