The development of acquired immunity to the prototypic facultative intracellular parasite L. monocytogenes is associated with T cell dependent production of macrophage activating factors. The immune mechanism as determined by adoptive transfer methods identifies the responding T cell population as members of the subset of cells expressing the Ly 1+2+ phenotype. It has also been established that this adoptively transferred immunity is short-lived. We have recently established that the interval of transferred immunity can be significantly lenghtened and resistance increased to levels comparable with that seen in actively immunized animals. This more active and longer lived cell population can be obtained from short term tissue culture of spleen cells obtained from immune donors. The dramatic increase in the level and duration of the passively acquired immune state is associated with a Ly 1+2- T cell subset with not apparent activity retained within the Ly 1+2+ cell population. Our proposed studies will focus on the nature of the immunoregulation that is responsible for the dramatic shift in the function and apparent phenotypic change of the cells obtained from the in vitro culture. For this analysis we will evaluate the culture conditions that lead to cells with enhanced transfer activity and will record the temporal appearance of transfer active cells in culture as well as the cell cycle and cell cooperation requirements. In additional studies we will investigate the interaction of the transfer active cells with the recipient environment. Finally, we will attempt to correlate the immunologic status of the donor with the appearance of enhanced transfer activity acquired by cells following in vitro culture.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI023455-01
Application #
3135559
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1985-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Providence Medical Center (Portland, OR)
Department
Type
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97213
Barry, Ronald A; Archie Bouwer, H G; Clark, Tina R et al. (2003) Protection of interferon-gamma knockout mice against Listeria monocytogenes challenge following intramuscular immunization with DNA vaccines encoding listeriolysin O. Vaccine 21:2122-32
Bouwer, H G; Barry, R A; Hinrichs, D J (2001) Lack of expansion of major histocompatibility complex class Ib-restricted effector cells following recovery from secondary infection with the intracellular pathogen Listeria monocytogenes. Infect Immun 69:2286-92
Cornell, K A; Bouwer, H G; Hinrichs, D J et al. (1999) Genetic immunization of mice against Listeria monocytogenes using plasmid DNA encoding listeriolysin O. J Immunol 163:322-9
Bouwer, H G; Shen, H; Fan, X et al. (1999) Existing antilisterial immunity does not inhibit the development of a Listeria monocytogenes-specific primary cytotoxic T-lymphocyte response. Infect Immun 67:253-8
Bouwer, H G; Bai, A; Forman, J et al. (1998) Listeria monocytogenes-infected hepatocytes are targets of major histocompatibility complex class Ib-restricted antilisterial cytotoxic T lymphocytes. Infect Immun 66:2814-7
Bouwer, H G; Barry, R A; Hinrichs, D J (1997) Acquired immunity to an intracellular pathogen: immunologic recognition of L. monocytogenes-infected cells. Immunol Rev 158:137-46
Bouwer, H G; Seaman, M S; Forman, J et al. (1997) MHC class Ib-restricted cells contribute to antilisterial immunity: evidence for Qa-1b as a key restricting element for Listeria-specific CTLs. J Immunol 159:2795-801
Bouwer, H G; Hinrichs, D J (1996) Cytotoxic-T-lymphocyte responses to epitopes of listeriolysin O and p60 following infection with Listeria monocytogenes. Infect Immun 64:2515-22
Bouwer, H G; Moors, M; Hinrichs, D J (1996) Elimination of the listeriolysin O-directed immune response by conservative alteration of the immunodominant listeriolysin O amino acid 91 to 99 epitope. Infect Immun 64:3728-35
Bouwer, H G; Gibbins, B L; Jones, S et al. (1994) Antilisterial immunity includes specificity to listeriolysin O (LLO) and non-LLO-derived determinants. Infect Immun 62:1039-45

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