Development, regulation and function of human natural killer cells in healthy and virus infected individuals

• Applicant: Dr. Nicole Marquardt
• Subject Area: Immunology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 212159925

Natural killer (NK) cells are part of the innate immune system and develop in humans already before birth. They play a major role in the defense of malignant and virus-infected cells and regulate the immune system by releasing high amounts of proinflammatory cytokines such as IFN-γ upon activation. NK cells are currently examined in particular for their influence and importance in hematopoietic stem cell transplantation (HSCT). Thus, the investigation of development and functional competence of NK cells are of special interest for their use in clinical settings. Although the developmental stages in adult individuals are well characterized so far, the distribution and functional capacities of NK cells in fetal organs are poorly understood. We suggest that NK cells from different organs display distinct developmental stages. Therefore, it is one of our major aims to characterize fetal NK cells in their phenotype and functions. We expect that the results of this study would contribute to the basic understanding of human NK cell development and the functional relevance of NK cells in the fetus. The data would also be of importance for further insights into clinical settings of in utero infections and transplantations. The second specific aim of this study will be the determination of the role of adult NK cells in HIV-1 infection. Again, NK cell development will be of special interest in this project, since activating and inhibitory NK cell receptors are expressed during NK cell maturation. Some of these surface receptors are critical for NK cell “licensing” and therefore the functional competence. We will address the question whether specific NK cell receptor expression patterns correlate to viral control in HIV-1 patients. Thus, the results would be of importance for the prediction of disease progression in HIV-1 infection.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Dr. Jakob Michaelsson