The overall goals of this project are to characterize cells of the murine immune system and determine the mechanism(s) of action and interaction among these cells in the generation and regulation of antibody responses in vitro to protein and synthetic amino acid antigens. Fluorescein conjugates of fowl gammaglobulin, hen egg lysozyme (HEL) and pigeon cytochrome C (PCC) and GAT will be used. A major unresolved problem in cellular immunlogy focuses on the nature of suppressor T cells (Ts cells). We have recently identified """"""""Ts cells"""""""" in the spleen of antigen-primed nude mice; this observation provides the means to better understand Ts cells, their development, mechanism(s) of activation and action and their role in regulation of antibody responses, especially to antigens under MHC-linked immune response gene (Ir gene) control, such as HEL, PCC and GAT. Ts subsets that have been identified in normal and nude mice are Ts cells in virgin spleen and suppressor-inducer and suppressor-effector Ts cells in antigen-primed spleen. The objectives of this proposal are to characterize """"""""Ts cells"""""""" in nude mice and compare them with Ts cells from normal mice in terms of: expression of membrane markers, such as Iat, Tind and Tsu; development and maturation; effects of thymus gland grafts on Ts cells in nude mice; effects of helper T cells on development of Ts cell subsets; and, antigen requirements for activation of Ts cells. We plan to determine the target cell and mechanism of action of products of these T cell subsets and to characterize membrane markers unique to Ts cell subsets (Iat, Tind and Tsu) by biochemical and molecular biological analysis. Lastly, we will clone these Ts cell subsets using a new procedure and characterize the clones by membrane markers, physiologic function and mechanism of action. These studies should provide new information on the origin, maturation, activation and mechanism of action of Ts cells and the characterization of unique markers expressed on T cells, such as Iat, Tind and Tsu. Since Ts cells are involved in the Ir gene control of responses to HEL, PCC and GAT, this study could provide new information concerning stimulation of helper and Ts cells by Ir gene controlled antigens in """"""""nonresponder"""""""" animals and the mechanism of action of Ir genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013915-18
Application #
3125572
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-09-01
Project End
1994-06-30
Budget Start
1992-09-01
Budget End
1994-06-30
Support Year
18
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Don and Sybil Harrington Cancer Center
Department
Type
DUNS #
City
Amarillo
State
TX
Country
United States
Zip Code
79118
Zimecki, M; Kapp, J A (1995) Presentation of antigen by B cell subsets. V. Effect of interleukin 7 (IL-7) and interleukin 10 (IL-10) on phenotype and antigen presenting function of immature B cells. Arch Immunol Ther Exp (Warsz) 43:253-7
Zimecki, M; Kapp, J A (1994) Presentation of antigen by B cell subsets. IV. Defective T-B cell signalling causes inability to present antigen by B cells from immunodeficient mice. Arch Immunol Ther Exp (Warsz) 42:361-7
Zimecki, M; Kapp, J A (1994) Presentation of antigen by B cell subsets. II. The role of CD5 B cells in the presentation of antigen to antigen-specific T cells. Arch Immunol Ther Exp (Warsz) 42:349-53
Zimecki, M; Kapp, J A (1994) Presentation of antigen by B cell subsets. III. Effects of interleukins on antigen presenting function and phenotype of immature B cells. Arch Immunol Ther Exp (Warsz) 42:355-9
Zimecki, M; Whiteley, P J; Pierce, C W et al. (1994) Presentation of antigen by B cells subsets. I. Lyb-5+ and Lyb-5- B cells differ in ability to stimulate antigen specific T cells. Arch Immunol Ther Exp (Warsz) 42:115-23
Kennedy, J D; Pierce, C W; Lake, J P (1992) Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice as a function of age. J Immunol 148:1620-9
Lake, J P; Pierce, C W; Kennedy, J D (1991) CD8+ alpha/beta or gamma/delta T cell receptor-bearing T cells from athymic nude mice are cytolytically active in vivo. J Immunol 147:1121-6
Devens, B H; Koontz, A W; Kapp, J A et al. (1991) Involvement of two distinct regulatory T cell populations in the antigen-specific suppression of cytolytic T cell generation. J Immunol 146:1394-401
Lake, J P; Pierce, C W; Kennedy, J D (1991) T cell receptor expression by T cells that mature extrathymically in nude mice. Cell Immunol 135:259-65
Kraig, E; Kannapell, C C; Zborowski, K A et al. (1990) Sequence of the TCR beta chain gene used by a T cell clone specific for the synthetic polymer, GAT. Nucleic Acids Res 18:5881

Showing the most recent 10 out of 28 publications