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Judith A. Woodfolk, MBChB, Ph.D. |
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Assistant Professor Of Research
Office:(434) 924-1293 Research Interest: Relevance of the Th1/Th2 Paradigm to Allergic Disease in Humans. Sensitization to allergens from diverse sources is a major risk factor for asthma. Studies on immunity associated with allergic and non-allergic responses are fundamental to understanding the pathogenesis of asthma and to the design of new treatments. Work in our laboratory focuses on T cell responses to intrinsic and extrinsic allergens in human-based in vitro systems. By skin testing and using serologic assays developed in the Allergy Division we can identify individuals with distinct immune responses to allergens. We have recently shown that different allergen-specific T cell repertoires mediate immediate hypersensitivity (IH) and delayed-type hypersensitivity (DTH) skin test reactions to the fungal allergen, Tri r 2. Paradoxically, DTH-associated major T cell epitopes induce Th2-dominated responses. This suggests that the immune response to allergens in humans does not adhere to the classical Th1/Th2 paradigm described in murine systems. Other studies in our laboratory focus on immune mechanisms of tolerance to the major cat allergen, Fel d 1. The modified Th2 response to cat allergen is characterized by the presence of Fel d 1-specific serum IgG/IgG4 antibodies without IgE in subjects exposed to high doses of allergen. This immune response is consistent with a form of tolerance based on the lack of an association with allergic symptoms or asthma. The regulatory cytokine, IL-10, has been implicated in allergen-specific T cell tolerance induced by systemic administration of antigen. The primary goal of ongoing studies is to elucidate the role of IL-10 in tolerance to cats induced by natural exposure to allergen via the respiratory tract. Our results suggest that IL-10 exerts regulatory effects on both allergic and non-allergic Fel d 1-specific T cell responses. In addition, we have identified major T cell epitopes of Fel d 1 which selectively induce IL-10 or IFN-g and which are a target for T cells induced early in the course of a conventional immunotherapy regimen. Such allergen-derived peptides which induce Th1 or regulatory cytokines are strong candidates for peptide vaccines. Selected Publications: Woodfolk JA, Sung SJ, Benjamin DC, Lee JK and Platts-Mills TAE: Different human T cell repertoires mediate immediate and delayed type hypersensitivity responses to the Trichophyton antigen, Tri r 2. J. Immunol., 165:4379-4387. 2000. Platts-Mills T, Vaughan J, Squillace S, Woodfolk JA, and Sporik R: Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet, 357:752-756. 2001. Woodfolk JA, Sung SJ, Ward GW, and Platts-Mills TAE: Immunodominant T cell epitopes associated with distinct immune responses to the dermatophyte antigen Tri r 2: statistical approaches to mapping studies. Int. Arch. Allergy Immunol., 124:90-92. 2001. Ludwig RJ, Woodfolk JA, Grundmann-Kollmann M, Enzensberger R, Runne U, Platts-Mills TAE, Kaufmann R, and Zollner TM: Chronic dermatophytosis in lamellar ichthyosis: relevance of a Th2 immune response to Trichophyton rubrum? [Letter]. Br. J. Dermatol., 145:518-521. 2001. Woodfolk JA, and Platts-Mills TAE: Diversity of the human allergen-specific T cell repertoire associated with distinct skin test reactions: DTH-associated major epitopes induce Th1- and Th2-dominated responses. J. Immunol., 167:5412-5419. 2001. Zollner TM, Podda M, Kaufmann R, Platts-Mills TAE, and Woodfolk JA: Increased incidence of skin infections in atopy: evidence for an antigen-specific homing defect [Review]. Clin. Exp. Allergy, 32:180-185. 2002. |
