The ultimate goal of these studies is to understand how exposing the skin of mice to ultraviolet radiation (UVR) leads to the production of suppressor T lymphocytes that inhibit the rejection of UVR-induced skin cancers. Specifically, we wish to define the cellular and molecular events that lead to suppression of immune responses in UV-irradiated mice. In the second competing renewal of this project, we propose to use lymphocytes from T cell receptor transgenic mice that express a clonotypic alpha beta T cell receptor specific for peptide 111 - 119 of influenza hemagglutinating antigen and the anti-clonotypic antibody 6.5 to follow the fate and activity of T cells in response to immunization in order to determine how this pathway is altered by UV irradiation of the host and whether T effector and suppressor cells arise from the same clonotypic T cell population. Second, we will continue our studies characterizing immune responses affected by the two pathways of UV-induced systemic immune suppression, one mediated by DNA damage the other by cis-urocanic acid. Third, we will further analyze the role of DNA damage in UV-induced alterations of cutaneous antigen-presenting cells. Approaches include using DNA repair deficient XPC knockout mice to increase DNA damage, and liposomes containing photolyases specific for UV photoproducts as a means of removing DNA damage. We will begin to define the mechanism(s) by which lesions in DNA inhibit APC function.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA052457-10
Application #
2894836
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Finerty, John F
Project Start
1990-07-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Ma, Lisa J; Guzman, Esther A; DeGuzman, Ariel et al. (2007) Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement. J Endocrinol 193:291-7
Maeda, Yutaka; Hwang-Verslues, Wendy W; Wei, Gang et al. (2006) Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene. Biochem J 400:303-13
Ma, Lisa J; Guzman, Esther A; DeGuzman, Ariel et al. (2006) Unexpected effects of UVB in IL-10 transgenic mice: normalization of contact hypersensitivity response. Arch Dermatol Res 297:417-20
Guzman, E A; Chen, Y-H; Langowski, J L et al. (2005) Abrogation of delayed type hypersensitivity response to Candida albicans produced by a molecular mimic of phosphorylated prolactin. J Neuroimmunol 170:31-40
Nishigori, C; Yarosh, D; O'Connor, A et al. (1998) HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and induce epidermal IL-10 in vitro. J Immunol 161:2684-91
Vink, A A; Moodycliffe, A M; Shreedhar, V et al. (1997) The inhibition of antigen-presenting activity of dendritic cells resulting from UV irradiation of murine skin is restored by in vitro photorepair of cyclobutane pyrimidine dimers. Proc Natl Acad Sci U S A 94:5255-60
Vink, A A; Yarosh, D B; Kripke, M L (1996) Chromophore for UV-induced immunosuppression: DNA. Photochem Photobiol 63:383-6
Vink, A A; Strickland, F M; Bucana, C et al. (1996) Localization of DNA damage and its role in altered antigen-presenting cell function in ultraviolet-irradiated mice. J Exp Med 183:1491-500
Nishigori, C; Yarosh, D B; Ullrich, S E et al. (1996) Evidence that DNA damage triggers interleukin 10 cytokine production in UV-irradiated murine keratinocytes. Proc Natl Acad Sci U S A 93:10354-9
Kripke, M L; Cox, P A; Bucana, C et al. (1996) Role of DNA damage in local suppression of contact hypersensitivity in mice by UV radiation. Exp Dermatol 5:173-80

Showing the most recent 10 out of 17 publications