Human mixed lymphocyte culture (MLC) can be used to generate natural killer (NK) or NK-like cytotoxicity. This cytotoxicity is not directed against alloantigens and can be generated from NK-inactive precursor cells. This research involves a detailed study of this phenomenon in order to determine the relationship of T-cell function to NK cytotoxicity. The experimental goals of the research include studies on the specificity of MLC-induced NK cytotoxicity by an analysis of reactivity against a large panel of target cells. Special emphasis will be given to reactivity against autochthonous biopsy obtained tumor cells. The phenotype of MLC-induced NK cells will be studied in order to determine the relationship of these cells to human T cells. The nature of the precursor cells required to generate this response will be examined both from the peripheral blood and from other lymphoid compartments such as the thymus. Preliminary data indicate that cytotoxic cells with NK activity can be generated from human thymocytes by allostimulation if interleukin-2 (IL-2) is present. This is an excellent model for studying the relationship of NK cells to T cells. Regulatory cells for the expression and induction of NK cytotoxicity will be further investigated. Our results indicate that cells capable of suppressing NK-effector function can be generated in vitro. These studies are designed to provide a more comprehensive understanding of the cell types involved in the generation of NK cytotoxicity, their relationship to T-cell functions, and their possible significance in human cancer. (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034442-03
Application #
3172118
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-02-01
Project End
1987-02-11
Budget Start
1986-02-01
Budget End
1987-02-11
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Dadmarz, R; Bockstoce, D C; Golub, S H (1994) Interleukin-7 selectively enhances natural kill cytotoxicity mediated by the CD56bright natural killer subpopulation. Lymphokine Cytokine Res 13:349-57
Shau, H; Gupta, R K; Golub, S H (1993) Identification of a natural killer enhancing factor (NKEF) from human erythroid cells. Cell Immunol 147:1-11
Iho, S; Shau, H; Golub, S H (1992) IL-6 enhances the cytotoxic activity of thymocyte-derived CD56+ cells. Cell Immunol 144:1-10
Shau, H; Kim, A; Golub, S H (1992) Modulation of natural killer and lymphokine-activated killer cell cytotoxicity by lactoferrin. J Leukoc Biol 51:343-9
Iho, S; Shau, H Y; Golub, S H (1991) Characteristics of interleukin-6-enhanced lymphokine-activated killer cell function. Cell Immunol 135:66-77
Ebina, N; Gallardo, D; Shau, H et al. (1990) IL-1 and IL-4 as reciprocal regulators of IL-2 induced lymphocyte cytotoxicity. Br J Cancer 62:619-23
Ibayashi, Y; Gray, J D; Golub, S H et al. (1990) The heterogeneity of target recognition by lymphokine-activated killer precursor cells. Jpn J Cancer Res 81:927-35
Shau, H Y; Golub, S H (1989) Inhibition of lymphokine-activated killer- and natural killer-mediated cytotoxicities by neutrophils. J Immunol 143:1066-72
Tokuda, Y; Ebina, N; Golub, S H (1989) The inhibitory effect of human interferon alpha on the generation of lymphokine-activated killer activity. Cancer Immunol Immunother 30:205-12
Shau, H; Gray, J D; Golub, S H (1988) Studies on cytotoxicity generated in human mixed lymphocyte culture. IV. Interleukin 2 alone or from mixed lymphocyte culture yields natural killer-like cytotoxic cells distinct from allospecific cytotoxic T lymphocytes. Cancer Immunol Immunother 27:255-60

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