The dissection of antigen-driven immunologic responses placed into the intricate multicompartmentalized framework of the in vivo environment presents a dimension of complexity that is not generally appreciated. This associates with the ability of lymphoid cells to recirculate and home and is best exemplified with cell-mediated immune responses where the imposition of a physical barrier between """"""""immune"""""""" cells and the stimulating antigen will totally abrogate a functional protective immune state. Therefore, the presence of accessory cells, the appropriate cellular interactions and collaborations, and the selection and differentiation of clonally-derived precursors for effector cells are insufficient for functional in vivo cell-mediated immune responses. The acquired or inherently induced capacity of lymphocytes to selectively extravasate into nonlymphoid sites of antigen deposition represents an essential component for effective in vivo immune function. To advance our understanding of syngeneic host-tumor interactions requires a full appreciation of selective lymphoid cell movement. This knowledge must be integrated into the already appreciated cellular interactions and responses that are taking place. Together, a more complete picture of the immunologic apparatus can be obtained and manipulated. The investigation of ultraviolet radiation (UVR) carcinogenesis has already provided us with an appreciation for the delicate interrelationship taking place among the host, the tumor, and the carcinogen (UVR). We have recently determined that one process mediated by this physical agent results in an induced alteration in lymphocyte recirculation pathways. This finding has direct immunologic implications. A detailed analysis of this phenomenon and its importance in antitumor immune responses represent the major objectives of this research. These studies will be complemented with experiments designed to address a number of basic questions associated with the nature and regulation of lymphocyte homing pathways. (SR)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025917-07
Application #
3167068
Study Section
Experimental Immunology Study Section (EI)
Project Start
1979-08-01
Project End
1989-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Zhang, Tian Y; Ding, Xiaohong; Daynes, Raymond A (2005) The expression of 11 beta-hydroxysteroid dehydrogenase type I by lymphocytes provides a novel means for intracrine regulation of glucocorticoid activities. J Immunol 174:879-89
Jones, Dallas C; Ding, Xiaohong; Zhang, Tian Y et al. (2003) Peroxisome proliferator-activated receptor alpha negatively regulates T-bet transcription through suppression of p38 mitogen-activated protein kinase activation. J Immunol 171:196-203
Daynes, Raymond A; Enioutina, Elena Y; Jones, Dallas C (2003) Role of redox imbalance in the molecular mechanisms responsible for immunosenescence. Antioxid Redox Signal 5:537-48
Jones, Dallas C; Ding, Xiaohong; Daynes, Raymond A (2002) Nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed in resting murine lymphocytes. The PPARalpha in T and B lymphocytes is both transactivation and transrepression competent. J Biol Chem 277:6838-45
Enioutina, Elena Y; Visic, Dino M; Daynes, Raymond A (2002) The induction of systemic and mucosal immunity to protein vaccines delivered through skin sites exposed to UVB. Vaccine 20:2116-30
Jones, Dallas C; Manning, Bernadette M; Daynes, Raymond A (2002) A role for the peroxisome proliferator-activated receptor alpha in T-cell physiology and ageing immunobiology. Proc Nutr Soc 61:363-9
Heithoff, D M; Enioutina, E Y; Daynes, R A et al. (2001) Salmonella DNA adenine methylase mutants confer cross-protective immunity. Infect Immun 69:6725-30
Manning, B M; Enioutina, E Y; Visic, D M et al. (2001) CpG DNA functions as an effective adjuvant for the induction of immune responses in aged mice. Exp Gerontol 37:107-26
Enioutina, E Y; Visic, V D; Daynes, R A (2000) Enhancement of common mucosal immunity in aged mice following their supplementation with various antioxidants. Vaccine 18:2381-93
Chen, X P; Ding, X; Daynes, R A (2000) Ganglioside control over IL-4 priming and cytokine production in activated T cells. Cytokine 12:972-85

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