The goal of this project is to determine the mechanisms of lymphocyte mediated cutaneous pathology in allergic contact dermatitis to urushiol (Toxicodendron radicans, """"""""poison ivy"""""""") and in drug eruptions. These conditions were chosen because the relevant antigen is known, lending them amenable to analysis. Both these conditions are a significant source of morbidity and economic loss. Allergic contact dermatitis is a leading cause of occupational disability and drug eruptions are a major source of morbidity in hospitalized patients. Lymphocyte function will be studied by the generation of IL2- dependent T-cell lines and clones from both peripheral blood and lesional skin of appropriate patients at various stages of their condition. Cultured T-cells will then be analyzed for phenotype, antigen specificity and function in a variety of in vitro assays. These techniques should reveal both the mechanisms of lymphocyte mediated pathology as well as its regulation. When applied to drug eruptions, these studies should be able to determine the relative role of drug (hapten) specific T-cells versus drug induced autoreactivity in the pathogenesis of this condition. It is hoped that these studies will lay the groundwork for future study of T-lymphocyte mediated conditions in which the inciting antigen is not known, such as sarcoidosis, lichen planus, and scleroderma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29AI026580-01
Application #
3454711
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Kalish, R S (1995) Antigen processing: the gateway to the immune response. J Am Acad Dermatol 32:640-52
Kalish, R S; LaPorte, A; Wood, J A et al. (1994) Sulfonamide-reactive lymphocytes detected at very low frequency in the peripheral blood of patients with drug-induced eruptions. J Allergy Clin Immunol 94:465-72
Kalish, R S; Wood, J A; LaPorte, A (1994) Processing of urushiol (poison ivy) hapten by both endogenous and exogenous pathways for presentation to T cells in vitro. J Clin Invest 93:2039-47
MacCarthy, K G; Blake, J S; Johnson, K L et al. (1994) Human dermatophyte-responsive T-cell lines recognize cross-reactive antigens associated with mannose-rich glycoproteins. Exp Dermatol 3:66-71
Kalish, R S; Johnson, K L; Hordinsky, M K (1992) Alopecia areata. Autoreactive T cells are variably enriched in scalp lesions relative to peripheral blood. Arch Dermatol 128:1072-7
Kalish, R S (1991) Recent developments in the pathogenesis of allergic contact dermatitis. Arch Dermatol 127:1558-63
Kalish, R S (1991) Drug eruptions: a review of clinical and immunological features. Adv Dermatol 6:221-37;discussion 238
Hordinsky, M K; Kalish, R S (1991) Autoreactive cells in alopecia areata. J Invest Dermatol 96:93S-94S
Kalish, R S (1990) The use of human T-lymphocyte clones to study T-cell function in allergic contact dermatitis to urushiol. J Invest Dermatol 94:108S-111S