Mechanism of natural killer cell mediated T cell cycle arrest during human parainfluenza virus type 3 infection
McQuaid, Samantha
(2013)
Mechanism of natural killer cell mediated T cell cycle arrest during human parainfluenza virus type 3 infection.
PhD thesis, Dublin City University.
Here we investigate the role of NK cells in inhibiting T cell cycle during Human Parainfluenza Virus type 3 (HPIV3) infection, attributing viral Hemagglutinin-neuraminidase (HN) to activation of this NK cell mediated T cell regulation via the NK cell receptors NKp44 and NKp46. Having associated HN with the induction of low level IL-2 production we demonstrated that low dose IL-2 expands primary human CD56bright NK cells resulting in contact dependent cell-cycle arrest of T cell proliferation. While this was true for the conventional T cell population, Tregs were actually promoted in these cultures. We also demonstrate by using blocking and activating antibodies that simultaneous activation of both NKp44 and NKP46 induce NK mediated cell cycle arrest in T cells at low IL-2 but that NKp44 alone is responsible for enhanced apoptosis in T cells at high IL-2. These results not only highlight the importance of NK cells in immune regulation but also identify key human therapeutic NK-targets for the future. In addition, these results may provide further insights into the therapeutic mechanisms of low dose IL-2 in autoimmunity. Finally, the possibility of isolated HPIV3 HN as a molecule for induction of this immune regulation is under investigation.