Bio

Bio


Research focus in T cell immunotherapy and T cell immune monitoring using high-throughput sequencing and genomic approaches, with an emphasis on hematopoietic stem cell transplantation, the treatment of graft-versus-host disease and immune tolerance induction.

Academic Appointments


Honors & Awards


  • Amy Streizer Manasevit Scholar, National Donor Marrow Program and American Society for Blood and Marrow Transplantation (2013)
  • Young Investigator Award, American Society of Blood and Marrow Transplantation (2011)

Research & Scholarship

Current Research and Scholarly Interests


Research focus in T cell immunotherapy and T cell immune monitoring using high-throughput sequencing and genomic approaches, with an emphasis on hematopoietic stem cell transplantation, the treatment of graft-versus-host disease and immune tolerance induction.

Teaching

Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


  • A distinct evolution of the T-cell repertoire categorizes treatment refractory gastrointestinal acute graft-versus-host disease BLOOD Meyer, E. H., Hsu, A. R., Liliental, J., Loehr, A., Florek, M., Zehnder, J. L., Strober, S., Lavori, P., Miklos, D. B., Johnson, D. S., Negrin, R. S. 2013; 121 (24): 4955-4962

    Abstract

    Steroid refractory gastrointestinal (GI) acute graft versus host disease (aGVHD) is a major cause of mortality in hematopoietic stem cell transplantation (HCT) without immune markers to establish a diagnosis or guide therapy. We found that T cell receptor β (TCRβ) CDR3 repertoire sequencing reveals patterns that could eventually serve as a disease biomarker of T cell alloreactivity in aGVHD. We identified T cell clones in GI biopsies in a heterogeneous group of 15 allogeneic HCT patients with GI aGVHD symptoms. Seven steroid-refractory aGVHD patients showed a more conserved TCRβ clonal structure between different biopsy sites in the GI tract than eight primary-therapy responsive patients. Tracking GI clones identified at endoscopy longitudinally in the blood also revealed an increased clonal expansion in patients with steroid-refractory disease. Immune repertoire sequencing-based methods could enable a novel personalized way to guide diagnosis and therapy in diseases where T cell activity is a major determinant.

    View details for DOI 10.1182/blood-2013-03-489757

    View details for Web of Science ID 000321896300024

  • Apoptotic Cells Activate NKT Cells through T Cell Ig-Like Mucin-Like-1 Resulting in Airway Hyperreactivity JOURNAL OF IMMUNOLOGY Lee, H., Meyer, E. H., Goya, S., Pichavant, M., Kim, H. Y., Bu, X., Umetsu, S. E., Jones, J. C., Savage, P. B., Iwakura, Y., Casasnovas, J. M., Kaplan, G., Freeman, G. J., DeKruyff, R. H., Umetsu, D. T. 2010; 185 (9): 5225-5235

    Abstract

    T cell Ig-like mucin-like-1 (TIM-1) is an important asthma susceptibility gene, but the immunological mechanisms by which TIM-1 functions remain uncertain. TIM-1 is also a receptor for phosphatidylserine (PtdSer), an important marker of cells undergoing programmed cell death, or apoptosis. We now demonstrate that NKT cells constitutively express TIM-1 and become activated by apoptotic cells expressing PtdSer. TIM-1 recognition of PtdSer induced NKT cell activation, proliferation, and cytokine production. Moreover, the induction of apoptosis in airway epithelial cells activated pulmonary NKT cells and unexpectedly resulted in airway hyperreactivity, a cardinal feature of asthma, in an NKT cell-dependent and TIM-1-dependent fashion. These results suggest that TIM-1 serves as a pattern recognition receptor on NKT cells that senses PtdSer on apoptotic cells as a damage-associated molecular pattern. Furthermore, these results provide evidence for a novel innate pathway that results in airway hyperreactivity and may help to explain how TIM-1 and NKT cells regulate asthma.

    View details for DOI 10.4049/jimmunol.1001116

    View details for Web of Science ID 000283248700036

    View details for PubMedID 20889552

  • Activation of nonclassical CD1d-restricted NK T cells induces airway hyperreactivity in beta(2)-microglobulin-deficient mice JOURNAL OF IMMUNOLOGY Koh, Y. I., Kim, H. Y., Meyer, E. H., Pichavant, M., Akbari, O., Yasumi, T., Savage, P. B., DeKruyff, R. H., Umetsu, D. T. 2008; 181 (7): 4560-4569

    Abstract

    Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in beta(2)-microglobulin (beta(2)m)(-/-) mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1(+) noninvariant TCR NKT cell population is present in beta(2)m(-/-) mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of beta(2)m(-/-) mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to alpha-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a beta(2)m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR.

    View details for Web of Science ID 000259755700018

    View details for PubMedID 18802058

  • ICOS/ICOSL interaction is required for CD4(+) invariant NKT cell function and homeostatic survival JOURNAL OF IMMUNOLOGY Akbari, O., Stock, P., Meyer, E. H., Freeman, G. J., Sharpe, A. H., Umetsu, D. T., DeKruyff, R. H. 2008; 180 (8): 5448-5456

    Abstract

    The development of airway hyperreactivity (AHR), a cardinal feature of asthma, requires the presence of invariant NKT (iNKT) cells. In a mouse model of asthma, we demonstrated that the induction of AHR required ICOS costimulation of iNKT cells. ICOS was highly expressed on both naive and activated iNKT cells, and expression of ICOS was greater on the CD4(+) iNKT than on CD4(-) iNKT cells. Furthermore, the number of CD4(+) iNKT cells was significantly lower in spleens and livers of ICOS(-/-) and ICOSL(-/-) mice, and the remaining iNKT cells in ICOS(-/-) mice were dysfunctional and failed to reconstitute AHR when adoptively transferred into iNKT cell-deficient Jalpha18(-/-) mice. In addition, direct activation of iNKT cells with alpha-GalCer, which induced AHR in wild-type mice, failed to induce AHR in ICOS(-/-) mice. The failure of ICOS(-/-) iNKT cells to induce AHR was due in part to an inability of the ICOS(-/-) iNKT cells to produce IL-4 and IL-13 on activation. Moreover, survival of wild-type iNKT cells transferred into ICOSL(-/-) mice was greatly reduced due to the induction of apoptosis. These results indicate that ICOS costimulation plays a major role in induction of AHR by iNKT cells and is required for CD4(+) iNKT cell function, homeostasis, and survival in the periphery.

    View details for Web of Science ID 000257506900033

    View details for PubMedID 18390727

  • Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17 JOURNAL OF EXPERIMENTAL MEDICINE Pichavant, M., Goya, S., Meyer, E. H., Johnston, R. A., Kim, H. Y., Matangkasombut, P., Zhu, M., Iwakura, Y., Savage, P. B., DeKruyff, R. H., Shore, S. A., Umetsu, D. T. 2008; 205 (2): 385-393

    Abstract

    Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell-deficient (CD1d(-/-) and Jalpha18(-/-)) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17(-/-) mice nor in WT mice treated with anti-IL-17 mAb. Thus, ozone exposure induces AHR that requires the presence of NKT cells and IL-17 production. Because NKT cells are required for the development of two very disparate forms of AHR (ozone- and allergen-induced), our results strongly suggest that NKT cells mediate a unifying pathogenic mechanism for several distinct forms of asthma, and represent a unique target for effective asthma therapy.

    View details for DOI 10.1084/jem.20071507

    View details for Web of Science ID 000253250300016

    View details for PubMedID 18250191

  • T cells and NKT cells in the pathogenesis of asthma ANNUAL REVIEW OF MEDICINE Meyer, E. H., DeKruyff, R. H., Umetsu, D. T. 2008; 59: 281-292

    Abstract

    Asthma is an immunological disease with multiple inflammatory and clinical phenotypes, characterized by symptoms of wheezing, shortness of breath, and coughing due to airway hyperreactivity (AHR) and reversible airway obstruction. In allergic asthma, the most common form of asthma, airway inflammation is mediated by adaptive immune recognition of protein allergens by Th2 cells, resulting in airway eosinophilia. However, in other forms of asthma, inflammation is associated with immune responses to respiratory infections and airway neutrophilia. A central feature common to all forms of asthma is AHR, the heightened responsiveness of the airways to nonspecific stimuli. AHR has been shown recently in animal models of asthma to require the presence of CD1d-restricted, invariant T cell receptor-positive, natural killer T (iNKT) cells. Although allergen-specific Th2 cells and iNKT cells have many phenotypic similarities (e.g., expression of CD4 and production of Th2 cytokines), they have complementary activities, such as production of Th2 cytokines under different conditions, differential sensitivity to corticosteroids, and responsiveness to different classes of antigen (proteins versus glycolipids). We hypothesize that Th2 cells and iNKT cells interact synergistically to induce asthma but that different forms of asthma result from distinct roles of CD4(+) iNKT cells versus Th2 cells.

    View details for DOI 10.1146/annurev.med.59.061506.154139

    View details for Web of Science ID 000253397600020

    View details for PubMedID 17937589

  • Delirium following abrupt discontinuation of fluoxetine CLINICAL NEUROLOGY AND NEUROSURGERY Blum, D., Maldonado, J., Meyer, E., Lansberg, M. 2008; 110 (1): 69-70

    Abstract

    Sudden discontinuation of serotonin reuptake inhibitors (SRI) can lead to a number of psychological (e.g., nervousness, anxiety, crying spells, psychomotor agitation, irritability, depersonalization, decreased mood, memory disturbances, confusion, decreased concentration, and/or slowed thinking) and somatic (e.g., nausea, dizziness, headache) symptoms. Recent studies have shown that withdrawal symptoms are common with paroxetine, venlafaxine and fluvoxamine, but relatively rare and mild with fluoxetine cessation, likely as a result of its longer half-life. We report an unusual case of a patient who developed delirium after abrupt discontinuation of fluoxetine.

    View details for DOI 10.1016/j.clineuro.2007.08.016

    View details for Web of Science ID 000252799500013

    View details for PubMedID 17913343

  • INKT cells require CCR4 to localize to the airways and to induce airway hyperreactivity JOURNAL OF IMMUNOLOGY Meyer, E. H., Wurbel, M., Staton, T. L., Pichavant, M., Kan, M. J., Savage, P. B., DeKruyff, R. H., Butcher, E. C., Campbell, J. J., Umetsu, D. T. 2007; 179 (7): 4661-4671

    Abstract

    iNKT cells are required for the induction of airway hyperreactivity (AHR), a cardinal feature of asthma, but how iNKT cells traffic to the lungs to induce AHR has not been previously studied. Using several models of asthma, we demonstrated that iNKT cells required the chemokine receptor CCR4 for pulmonary localization and for the induction of AHR. In both allergen-induced and glycolipid-induced models of AHR, wild-type but not CCR4-/- mice developed AHR. Furthermore, adoptive transfer of wild-type but not CCR4-/- iNKT cells reconstituted AHR in iNKT cell-deficient mice. Moreover, we specifically tracked CCR4-/- vs wild-type iNKT cells in CCR4-/-:wild-type mixed BM chimeric mice in the resting state, and when AHR was induced by protein allergen or glycolipid. Using this unique model, we showed that both iNKT cells and conventional T cells required CCR4 for competitive localization into the bronchoalveolar lavage/airways compartment. These results establish for the first time that the pulmonary localization of iNKT cells critical for the induction of AHR requires CCR4 expression by iNKT cells.

    View details for Web of Science ID 000249752100043

    View details for PubMedID 17878364

  • iNKT cells in allergic disease T CELL ACTIVATION BY CD1 AND LIPID ANTIGENS Meyer, E. H., DeKruyff, R. H., Umetsu, D. T. 2007; 314: 269-291

    Abstract

    Recent studies indicate that invariant TCR+ CD1d-restricted natural killer T (iNKT) cells play an important role in regulating the development of asthma and allergy. iNKT cells can function to skew adaptive immunity toward Th2 responses, or can act directly as effector cells at mucosal surfaces in diseases such as ulcerative colitis and bronchial asthma. In mouse models of asthma, NKT cell-deficient strains fail to develop allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma, and NKT cells are found in the lungs of patients with chronic asthma, suggesting a critical role for NKT cells in the development of AHR. However, much work remains in characterizing iNKT cells and their function in asthma, and in understanding the relationship between the iNKT cells and conventional CD4+ T cells.

    View details for Web of Science ID 000247882800011

    View details for PubMedID 17593665

  • Natural killer T cells regulate the development of asthma INTERNATIONAL REVIEWS OF IMMUNOLOGY Umetsu, D. T., Meyer, E. H., DeKruyff, R. H. 2007; 26 (1-2): 121-140

    View details for DOI 10.1080/08830180601070237

    View details for Web of Science ID 000244119100007

    View details for PubMedID 17454267

  • CD1d restricted natural killer T cells are not required for allergic skin inflammation JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Elkhal, A., Pichavant, M., He, R., Scott, J., Meyer, E., Goya, S., Geha, R. S., Umetsu, D. T. 2006; 118 (6): 1363-1368

    Abstract

    Invariant T-cell receptor-positive natural killer (iNKT) cells have been shown to be essential for the development of allergen-induced airway hyperreactivity (AHR).We examined the role of iNKT cells in allergic skin inflammation using a murine model of atopic dermatitis (AD) elicited by epicutaneous sensitization with ovalbumin (OVA).Wild-type (WT) and natural killer T-cell-deficient CD1d-/- mice were epicutaneously sensitized with OVA or normal saline and challenged with aerosolized OVA. iNKT cells in skin and bronchoalveolar lavage fluid were analyzed by fluorescence-activated cell sorting, and cytokine mRNA levels were measured by quantitative RT-PCR. AHR to methacholine was measured after OVA inhalation.Skin infiltration by eosinophils and CD4+ cells and expression of mRNA encoding IL-4 and IL-13 in OVA-sensitized skin were similar in WT and CD1d-/- mice. No significant increase in iNKT cells was detectable in epicutaneously sensitized skin. In contrast, iNKT cells were found in the bronchoalveolar lavage fluid from OVA-challenged epicutaneously sensitized WT mice, but not CD1d-/- mice. Epicutaneously sensitized CD1d-/- mice had an impaired expression of IL-4, IL-5, and IL-13 mRNA in the lung and failed to develop AHR in response to airway challenge with OVA.These results demonstrate that iNKT cells are not required for allergic skin inflammation in a murine model of AD, in contrast with airway inflammation, in which iNKT cells are essential.Understanding the potential role of iNKT cells in AD will allow us to have a more specific target for therapeutic use.

    View details for DOI 10.1016/j.jaci.2006.08.010

    View details for Web of Science ID 000242880300025

    View details for PubMedID 17157667

  • Medicine on a need-to-know basis NATURE IMMUNOLOGY Busch, R., Byrne, B., Gandrud, L., Sears, D., Meyer, E., Kattah, M., Kurihara, C., Haertel, E., Parnes, J. R., Mellins, E. D. 2006; 7 (6): 543-547

    Abstract

    Disease-oriented, introductory medical curricula can help overcome educational and institutional barriers that separate aspiring translational scientists in PhD programs from the world of medicine.

    View details for Web of Science ID 000237751200004

    View details for PubMedID 16715061

  • Glycolipid activation of invariant T cell receptor(+) NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4(+) T cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Meyer, E. H., Goya, S., Akbari, O., Berry, G. J., Savage, P. B., Kronenberg, M., Nakayama, T., DeKruyff, R. H., Umetsu, D. T. 2006; 103 (8): 2782-2787

    Abstract

    Asthma is an inflammatory lung disease, in which conventional CD4+ T cells producing IL-4/IL-13 appear to play an obligatory pathogenic role. Here we show, in a mouse model of asthma, that activation of pulmonary IL-4/IL-13 producing invariant TCR+ CD1d-restricted natural killer T (NKT) cells is sufficient for the development of airway hyperreactivity (AHR), a cardinal feature of asthma, in the absence of conventional CD4+ T cells and adaptive immunity. Respiratory administration of glycolipid antigens that specifically activate NKT cells (alpha-GalactosylCeramide and a Sphingomonas bacterial glycolipid) rapidly induced AHR and inflammation typically associated with protein allergen administration. Naïve MHC class II-deficient mice, which lack conventional CD4+ T but have NKT cells, showed exaggerated baseline AHR and, when challenged with alpha-GalactosylCeramide, demonstrated even greater AHR. These studies demonstrate an expanded role for NKT cells, in which NKT cells not only produce cytokines that influence adaptive immunity but also function as critical effector cells that can induce AHR. These results suggest that NKT cells responding to glycolipid antigens, as well as conventional CD4+ T cells responding to peptide antigens, may be synergistic in the induction of AHR, although in some cases, each may independently induce AHR.

    View details for DOI 10.1073/pnas.0510282103

    View details for Web of Science ID 000235554900055

    View details for PubMedID 16478801

  • Adaptation at specific loci. VII. Natural selection, dispersal and the diversity of molecular-functional variation patterns among butterfly species complexes (Colias : Lepidoptera, Pieridae) MOLECULAR ECOLOGY Watt, W. B., Wheat, C. W., Meyer, E. H., Martin, J. F. 2003; 12 (5): 1265-1275

    Abstract

    Natural genetic variants at the phosphoglucose isomerase, PGI, gene differ in spatial patterning of their polymorphism among species complexes of Colias butterflies in North America. In both lowland and alpine complexes, molecular-functional properties of the polymorphic genotypes can be used to predict genotype-specific adult flight performances and resulting large genotypic differences in adult fitness components. In the lowland species complex, there is striking uniformity of PGI polymorph frequencies at a number of sites across the American West; this fits with earlier findings of strong, similar differences in fitness components over this range. In an alpine complex, Colias meadii shows similar uniformity of PGI frequencies within habitat types, either montane steppe or alpine tundra, over several hundred kilometres in the absence of dispersal. At the same time, large shifts (10-20%) in frequency of the most common alleles occur between steppe and tundra populations, whether these are isolated or, as in some cases, are in contact and exchange many dispersing adults each generation. Data on male mating success of common C. meadii PGI genotypes in steppe and tundra show heterozygote advantage in both habitat types, with shifts in relative homozygote disadvantage between habitats which are consistent with observed frequency differences. Nonadaptive explanations for this situation are rejected, and alternative, thermal-ecology-based adaptive hypotheses are proposed for later experimental test. These findings show that strong local selection may dominate dispersal as an evolutionary agent, whether or not dispersal is present, and that selection may often be the major force promoting 'cohesion' of species over long distances. This case offers new opportunities for integrating studies of molecular structure and function with ecological aspects of natural selection in the wild, both within and among species.

    View details for Web of Science ID 000182261500015

    View details for PubMedID 12694289

  • Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity NATURE MEDICINE Akbari, O., Stock, P., Meyer, E., Kronenberg, M., Sidobre, S., Nakayama, T., Taniguchi, M., Grusby, M. J., DeKruyff, R. H., Umetsu, D. T. 2003; 9 (5): 582-588

    Abstract

    Using natural killer T (NKT) cell-deficient mice, we show here that allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma, does not develop in the absence of V(alpha)14i NKT cells. The failure of NKT cell-deficient mice to develop AHR is not due to an inability of these mice to produce type 2 T-helper (Th2) responses because NKT cell-deficient mice that are immunized subcutaneously at non-mucosal sites produce normal Th2-biased responses. The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281(-/-) mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d(-/-) mice of recombinant IL-13, which directly affects airway smooth muscle cells. Thus, pulmonary V(alpha)14i NKT cells crucially regulate the development of asthma and Th2-biased respiratory immunity against nominal exogenous antigens. Therapies that target V(alpha)14i NKT cells may be clinically effective in limiting the development of AHR and asthma.

    View details for DOI 10.1038/nm851

    View details for Web of Science ID 000182610600040

    View details for PubMedID 12669034

  • CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Oh, J. W., Seroogy, C. M., Meyer, E. H., Akbari, O., Berry, G., Fathman, C. G., DeKruyff, R. H., Umetsu, D. T. 2002; 110 (3): 460-468

    Abstract

    T(H)2 cells play a critical role in the pathogenesis of asthma, but the precise immunologic mechanisms that inhibit T(H)2 cell function in vivo are not well understood.The purpose of our studies was to determine whether T cells producing IL-10 regulate the development of asthma.We used gene therapy to generate ovalbumin-specific CD4 T-helper cells to express IL-10, and we examined their capacity to regulate allergen-induced airway hyperreactivity.We demonstrated that the CD4 T-helper cells engineered to express IL-10 abolished airway hyperreactivity and airway eosinophilia in BALB/c mice sensitized and challenged with ovalbumin and in SCID mice reconstituted with ovalbumin-specific T(H)2 effector cells. The inhibitory effect of the IL-10-secreting T-helper cells was accompanied by the presence of increased quantities of IL-10 in the bronchoalveolar lavage fluid, was antigen-specific, and was reversed by neutralization of IL-10. Moreover, neutralization of IL-10 by administration of anti-IL-10 mAb in mice sensitized and challenged with ovalbumin seriously exacerbated airway hyperreactivity and airway inflammation.Our results demonstrate that T cells secreting IL-10 in the respiratory mucosa can indeed regulate T(H)2-induced airway hyperreactivity and inflammation, and they strongly suggest that IL-10 plays an important inhibitory role in allergic asthma.

    View details for DOI 10.1067/mai.2002.127512

    View details for Web of Science ID 000177936900018

    View details for PubMedID 12209095

  • Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity NATURE MEDICINE Akbari, O., Freeman, G. J., Meyer, E. H., Greenfield, E. A., Chang, T. T., Sharpe, A. H., Berry, G., DeKruyff, R. H., Umetsu, D. T. 2002; 8 (9): 1024-1032

    Abstract

    Asthma is caused by T-helper cell 2 (Th2)-driven immune responses, but the immunological mechanisms that protect against asthma development are poorly understood. T-cell tolerance, induced by respiratory exposure to allergen, can inhibit the development of airway hyperreactivity (AHR), a cardinal feature of asthma, and we show here that regulatory T (T(R)) cells can mediate this protective effect. Mature pulmonary dendritic cells in the bronchial lymph nodes of mice exposed to respiratory allergen induced the development of T(R) cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS-ICOS-ligand pathway. The T(R) cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, T(R) cells blocked the development of AHR. Both the development and the inhibitory function of regulatory cells were dependent on the presence of IL-10 and on ICOS-ICOS-ligand interactions. These studies demonstrate that T(R) cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma.

    View details for DOI 10.1038/nm745

    View details for Web of Science ID 000177757900039

    View details for PubMedID 12145647

Conference Proceedings


  • Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17 Pichavant, M., Goya, S., Meyer, E., Johnston, R., Kim, H., Matangkasombut, P., Zhu, M., Iwakura, Y., Savage, P., DeKruyff, R., Shore, S., Umetsu, D. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2008: S38-S38
  • iNKT-Cells require CCR4 binding of CCL17 to localize to the airways where they are necessary and sufficient for inducing airway hyperreactivity. Meyer, E., Wurbel, M., Staton, T., Savage, P., DeKruyff, R., Campbell, J., Butcher, E., Umetsu, D. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2006: S22-S22
  • Glycolipid mediated activation of iNKT cells is sufficient to induce airway hyperreactivity independent of conventional CD4 T cells. Meyer, E. H., Akbari, O., Berry, G., Savage, P., DeKruyff, R. H., Umetsu, D. T. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2005: S14-S15

Stanford Medicine Resources: