Abstract

The objective of this proposal is to determine the role of costimulatory signals (CD28/B7, CD40L/CD40) in the pathogenesis of allergic airway inflammation and hyperresponsiveness (AHR). We have found that inhibition of T cell activation with CTLA4-Ig (a fusion protein which blocks costimulation) prevents the induction of allergic AHR in a murine model. Our hypothesis is that costimulatory signals are critical in the development of allergen induced AHR. We will dissect the mechanisms by which costimulatory molecules regulate allergen induced AHR using transgenic knock-out mice, fusion proteins and monoclonal antibodies. As appropriate, we will compare our findings from the model of allergen induced pulmonary inflammation to a model of contact hypersensitivity (CHS). Thus, paradigms learned from these models with interruption of costimulation may be applicable to other T cell mediated diseases, including other skin diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR042689-05
Application #
2779069
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Tian, Tian; Jin, Michelle Qiushuang; Dubin, Krista et al. (2017) IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection. J Immunol 198:4341-4351
Pan, Youdong; Tian, Tian; Park, Chang Ook et al. (2017) Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature 543:252-256
Volpicelli, Elgida R; Lezcano, Cecilia; Zhan, Qian et al. (2014) The multidrug-resistance transporter ABCB5 is expressed in human placenta. Int J Gynecol Pathol 33:45-51
Guenova, Emmanuella; Watanabe, Rei; Teague, Jessica E et al. (2013) TH2 cytokines from malignant cells suppress TH1 responses and enforce a global TH2 bias in leukemic cutaneous T-cell lymphoma. Clin Cancer Res 19:3755-63
Majewska-Szczepanik, Monika; Paust, Silke; von Andrian, Ulrich H et al. (2013) Natural killer cell-mediated contact sensitivity develops rapidly and depends on interferon-?, interferon-? and interleukin-12. Immunology 140:98-110
Zadran, Sohila; McMickle, Robert; Shackelford, David et al. (2013) Monitoring extra-vascular migratory metastasis (EVMM) of migrating cancer cells using an in vitro co-culture system. Protoc exch 2013:
Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen et al. (2013) Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells. J Clin Invest 123:3756-65
Dowlatshahi, Mitra; Huang, Victor; Gehad, Ahmed E et al. (2013) Tumor-specific T cells in human Merkel cell carcinomas: a possible role for Tregs and T-cell exhaustion in reducing T-cell responses. J Invest Dermatol 133:1879-89
Degen, Martin; Natarajan, Easwar; Barron, Patricia et al. (2012) MAPK/ERK-dependent translation factor hyperactivation and dysregulated laminin ýý2 expression in oral dysplasia and squamous cell carcinoma. Am J Pathol 180:2462-78
Tian, Tian; Dubin, Krista; Jin, Qiushuang et al. (2012) Disruption of TNF-?/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection. J Invest Dermatol 132:1425-34

Showing the most recent 10 out of 113 publications