and/or aims): The major portion of the study is based on the applicant's previous work demonstrating that coincubation of Ia+ murine keratinocytes with syngeneic T cell clones results in prolonged antigen specific T cell tolerance. Although the mechanism by which """"""""aberrant"""""""" accessory cells produce T cell anergy is not completely understood, it apparently is due to their inability to provide an as yet uncharacterized second signal. Production of clonal anergy by presentation of antigen on """"""""aberrant"""""""" accessory cells appears to be operative in mice in-vivo as well. Thus, if such a method of T cell unresponsiveness induction could be produced in humans, it would have important ramifications for the treatment of T cell mediated hypersensitivity diseases such as allergic contact dermatitis. While human T cell tolerance has been produced in humans before, there have been no studies to determine whether clonal anergy can be produced in human T cells. This is important since there are several mechanisms (suppressor T cell, clonal deletion, clonal anergy) by which T cells can be made unresponsive. The three specific aims propose to study the immunobiology of human T cell clonal anergy, to examine the phenotypic and functional changes in T cells associated with its induction, and to determine whether anergic T cells have abnormalities in their activation pathways. Establishment of such an in-vivo model of T cell unresponsiveness should provide the theoretical basis for attempts to induce unresponsiveness in-vivo in patients with allergic diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AR040933-03
Application #
3457544
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Burns Jr, R P; Nasir, A; Haake, A R et al. (1999) B7-1 overexpression by thymic epithelial cells results in transient and long-lasting effects on thymocytes and peripheral T helper cells but does not result in immunodeficiency. Cell Immunol 194:162-77
Gaspari, A A; Burns, R; Nasir, A et al. (1998) CD86 (B7-2), but not CD80 (B7-1), expression in the epidermis of transgenic mice enhances the immunogenicity of primary cutaneous Candida albicans infections. Infect Immun 66:4440-9
Yeh, K Y; Chen, Z; Nasir, A et al. (1997) Expression of B7-1 by Pam 212 squamous cell carcinoma enhances tumor cell interactions with dendritic epidermal cells but does not affect in vivo tumor growth. J Invest Dermatol 109:728-33
Gaspari, A A; Zalka, A D; Payne, D et al. (1997) Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia. Arch Dermatol 133:491-6
Gaspari, A A (1996) Mechanisms of resolution of allergic contact dermatitis. Am J Contact Dermat 7:212-9
Burns Jr, R P; Gaspari, A A (1996) The use of transgenic mouse models to investigate the immune mechanisms of allergic contact dermatitis: an area of emerging opportunities. Am J Contact Dermat 7:120-30
Nasir, A; Gaspari, A A (1996) Contact dermatitis. Clinical perspectives and basic mechanisms. Clin Rev Allergy Immunol 14:151-84
Asnis, L A; Gaspari, A A (1995) Cutaneous reactions to recombinant cytokine therapy. J Am Acad Dermatol 33:393-410;quiz 410-2
Nasir, A; Ferbel, B; Gaspari, A A (1995) Human keratinocytes regulate their expression of B7/BB-1 antigen by a unique, calcium-dependent mechanism. J Invest Dermatol 104:763-7
Yeh, K Y; Pulaski, B A; Woods, M L et al. (1995) B7-1 enhances natural killer cell-mediated cytotoxicity and inhibits tumor growth of a poorly immunogenic murine carcinoma. Cell Immunol 165:217-24

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