There is strong evidence that the destruction of syngeneic tumors may be mediated by at least three distinct effector mechanisms that involve T cells, null cells, and macrophages as the effectors. There is also evidence that each of these effector mechanisms can be, and are, suppressed in tumor-bearing hosts by suppressive factors released by the tumors or by suppressor cells induced by direct contact with tumors. The objective of this project is to examine the interactions of phenotypically distinct subpopulations of cells that are involved in the generation and suppression of three different immune mechanisms effecting the destruction of syngeneic tumors. The basic approach is to examine the mechanism of generation of effectors and suppressors of tumor destruction with key focus being on the identification of distinct differentiation and activation lymphokines and phenotypic identification and isolation of the cells producing the factors. The interaction of the helper and suppressor systems will be examined in the context of whether the suppressor factors interfere with production of, or responsiveness to, the differentiation or activation factors of the cytotoxic effectors of tumor destruction and vice versa. The goal is to reveal contrasuppressive interactions that would reduce the suppressive influence of syngeneic tumors on the immune system. (MB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038408-03
Application #
3176542
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-12-01
Project End
1987-06-30
Budget Start
1986-01-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
East Tennessee State University
Department
Type
Schools of Medicine
DUNS #
City
Johnson City
State
TN
Country
United States
Zip Code
37614
Suttles, J; Miller, R W; Tao, X et al. (1994) T cells which do not express membrane tumor necrosis factor-alpha activate macrophage effector function by cell contact-dependent signaling of macrophage tumor necrosis factor-alpha production. Eur J Immunol 24:1736-42
Tao, X; Stout, R D (1993) T cell-mediated cognate signaling of nitric oxide production by macrophages. Requirements for macrophage activation by plasma membranes isolated from T cells. Eur J Immunol 23:2916-21
Stout, R D; Suttles, J (1993) T cell-macrophage cognate interaction in the activation of macrophage effector function by Th2 cells. J Immunol 150:5330-7
Stout, R D; Suttles, J (1992) Evidence for involvement of TNF-alpha in the induction phase and IFN-beta in the effector phase of antiproliferative activity of splenic macrophages. Cell Immunol 139:363-74
Stout, R D; Bottomly, K (1989) Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages. J Immunol 142:760-5
Stout, R D; Suttles, J (1988) Problems and applications of cell cycle analysis: distinguishing G0 from G1 and G1 from S phase. Cytometry Suppl 3:34-7
Stout, R D; Schwarting, G A; Suttles, J (1987) Evidence that expression of asialo-GM1 may be associated with cell activation. Correlation of asialo-GM1 expression with increased total cellular RNA and protein content in normal thymocyte and spleen cell populations. J Immunol 139:2123-9
Stout, R D; Suttles, J (1987) Functional characteristics of in vitro generated macrophages: a transient refractory state precedes reinducibility of a spatially restricted, possibly contact-dependent, cytostatic mechanism. Cell Immunol 105:33-44
Suttles, J; Schwarting, G A; Hougland, M W et al. (1987) Expression of asialo GM1 on a subset of adult murine thymocytes: histological localization and demonstration that the asialo GM1-positive subset contains both the functionally mature and the proliferating thymocyte subpopulations. J Immunol 138:364-72
Suttles, J; Schwarting, G A; Stout, R D (1986) Flow cytometric analysis reveals the presence of asialo GM1 on the surface membrane of alloimmune cytotoxic T lymphocytes. J Immunol 136:1586-91

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