Mody, ChristopherKyei, Stephen Kofi2015-04-302015-06-222015-04-302015Kyei, S. K. (2015). IL-12 Restores Defective NK Cell Anticryptococcal Activity in HIV-Infected Patients (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26443http://hdl.handle.net/11023/2191Cryptococcus neoformans is a pathogenic yeast that causes life-threatening pneumonia and meningitis in AIDS patients. Natural killer (NK) cells are important effector cells that directly recognize and kill C. neoformans via perforin-dependent cytotoxicity. Although it had previously been demonstrated that, NK cells from HIV-infected patients have defective anticryptococcal activity, and IL-12 restored the activity, almost nothing was known of the mechanisms causing this defect or how IL-12 restored the defect. By examining the sequential steps in NK cell killing of Cryptococcus, I determined that NK cells from HIV-infected patients had lower intracellular perforin expression, defective perforin release and defective ability to polarize perforin to the fungal synapse. Importantly, treatment of NK cells from HIV-infected patients with IL-12 reversed these defects and restored the defective anticryptococcal activity. Thus, there are multiple defects in the cytolytic machinery of NK cells from HIV-infected patients, which result in the defective anticryptococcal activity, and these defects can be reversed with IL-12.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.ImmunologyCryptococcusHIVNK cellsInterleukinmaster thesis10.11575/PRISM/26443