Our studies on tumor immunity in vitro and in vivo led to the observation that macrophages were generated in vivo in tumor bearing mice and in vitro in spleen cell cultures. The macrophages are generated in several stages involving radiosensitive and radio- resistant maturation. They can be activated to inhibit tumor cell growth in a local or contact dependent manner and can be activated to produce monokines required for cellular immune responses. T cells can activate the macrophages by direct recognition of allo- MHC determinants or by recognition of antigen in association with self determinants. Using T cell clones, flow cytometric sorting of cells from primary lymphoid tissue, and in vitro culture techniques, functionally distinct and maturationally distinct T cell subpopulations are being evaluated for their ability to activate monokine production and cytostatic activity in the macrophage population and to become activated to produce lymphokines. The role of cognate and non-cognate T cell-macrophage interactions in inducing these effector functions and in amplifying cellular immune reactions are being investigated.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA038408-04A2
Application #
3176540
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-12-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
4
Fiscal Year
1988
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
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
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; 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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