The long range objective of this project is to identify the role of one of the major effector cell types of non-adaptive immunity, the natural killer (NK) cells, in the general mechanisms of resistance of the organism. The working hypothesis derived from our research and that of others is that a) human NK cells represent a relatively homogenous discrete cell type, with various defensive and regulatory activities including, but not limited to cell mediated cytotoxicity; b) NK cells effectiveness and specificity in vivo depends on a complex network of interaction with humoral factors and other cellular types that can be effectively analyzed in in vitro experiments; c) some of the regulatory and functional mechanisms of NK cells, as well as surface molecules, are similar but not necessarily identical to those of cytotoxic T cells and of myelomonocytic cells. In order to analyze this hypothesis and to further our understanding of the lineage, function, and regulation of human NK cells we propose to continue the characterization of the surface phenotype of human NK cells, to analyze the ability of NK cells to produce lymphokines, to investigate the role of surface interactions and secretion in the mechanism of cytotoxicity, to study activation and growth of NK cells, and to characterize NK precursor cells.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wistar Institute
United States
Zip Code
Brando, Clara; Mukhopadhyay, Sunil; Kovacs, Eniko et al. (2005) Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104. J Leukoc Biol 78:359-71
Gomez, German G; Read, Susana B; Gerschenson, Lazaro E et al. (2004) Interactions of the allogeneic effector leukemic T cell line, TALL-104, with human malignant brain tumors. Neuro Oncol 6:83-95
Wysocka, Maria; Zaki, Mohamed H; French, Lars E et al. (2002) Sezary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines. Blood 100:3287-94
Wysocka, M; Robertson, S; Riemann, H et al. (2001) IL-12 suppression during experimental endotoxin tolerance: dendritic cell loss and macrophage hyporesponsiveness. J Immunol 166:7504-13
Trinchieri, G; Scott, P (1999) Interleukin-12: basic principles and clinical applications. Curr Top Microbiol Immunol 238:57-78
Marshall, J D; Chehimi, J; Gri, G et al. (1999) The interleukin-12-mediated pathway of immune events is dysfunctional in human immunodeficiency virus-infected individuals. Blood 94:1003-11
Kubin, M Z; Parshley, D L; Din, W et al. (1999) Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48. Eur J Immunol 29:3466-77
Fox, F E; Kubin, M; Cassin, M et al. (1999) Retinoids synergize with interleukin-2 to augment IFN-gamma and interleukin-12 production by human peripheral blood mononuclear cells. J Interferon Cytokine Res 19:407-15
Monteiro, J M; Harvey, C; Trinchieri, G (1998) Role of interleukin-12 in primary influenza virus infection. J Virol 72:4825-31
Schwarz, A; Grabbe, S; Grosse-Heitmeyer, K et al. (1998) Ultraviolet light-induced immune tolerance is mediated via the Fas/Fas-ligand system. J Immunol 160:4262-70

Showing the most recent 10 out of 107 publications