Parsons, Matthew S. (Matthew Sidney) (2010) Looks that kill: accessory receptor phenotypes and the cytolytic activities of cytotoxic T-lymphocytes and natural killer cells. Masters thesis, Memorial University of Newfoundland.
- Accepted Version
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Natural killer (NK) cells and cytotoxic T-lymphocytes (CTL) express activating and inhibitory accessory receptors specific for class I human leukocyte antigens (HLA-I) or stress induced antigens. Signals from the ligation of these receptors are integrated to modulate T-cell mediated cytolysis and to determine NK cell cytolytic activity. Signals generated from the ligation of inhibitory receptors also mediate several other functions, such as reducing apoptosis and activation induced cell death. In mouse models these inhibitory receptors 'license' NK cells. NK cells expressing an inhibitory receptor, from mice expressing the ligand, have the ability to mediate both general and antibody-dependent cellular cytotoxicity (ADCC). NK 'licensing' also appears to account for human NK cell activity. Data from two studies have demonstrated a role for licensing of general NK cell mediated cytolysis, but data regarding ADCC are conflicting. As activating and inhibitory receptors are of much importance to both NK and T-cells, we investigated the potential expression and/or involvement of these receptors in the HLA-I unrestricted cytolysis mediated against CD4⁺ T-lymphocytes by a subset of CD8⁺ CTL in HIV infection. The TCR-dependent and HLA-I-independent CTL demonstrated a phenotype that matches generalized changes on CD8⁺ T-lymphocytes in progressive HIV infection. The CTL that killed activated uninfected CD4⁺ T-lymphocytes lacked expression of the CD56 marker and the inhibitory NKG2A receptor. We also investigated the role of NK cell 'licensing' for ADCC in humans. The potency of NK cells expressing the inhibitory KIR3DL1 receptor was investigated in samples taken from individuals expressing and not expressing the HLA-BW4 ligand. Our results suggest NK cell licensing is involved in ADCC.
|Item Type:||Thesis (Masters)|
|Additional Information:||Includes bibliographical references|
|Department(s):||Medicine, Faculty of|
|Library of Congress Subject Heading:||Cell-mediated cytotoxicity; Killer cells; T cells--Receptors|
|Medical Subject Heading:||Antibody-Dependent Cell Cytotoxicity; Killer Cells, Natural; T-Lymphocytes, Cytotoxic|
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