Oral Presentation 9th Australasian Virology Society Meeting 2017

EXPANSION OF NKG2C+ NATURAL KILLER CELLS FOLLOWING CMV INFECTION POST LUNG TRANSPLANT (#34)

Christopher M Harpur 1 , Sanda Stankovic 1 , Andrew G Brooks 1 , Glen P Westall 2 , Lucy C Sullivan 1
  1. The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  2. The Alfred Hospital, Melbourne, VIC, Australia

In healthy individuals cytomegalovirus (CMV) typically induces asymptomatic disease, whereas in lung transplant recipients immunosuppressive medications result in impaired antiviral immunity and a propensity for CMV reactivation within the lung allograft. As such, the control of CMV is a significant hurdle to successful lung transplantation. In healthy individuals, natural killer (NK) cells play a key role in immunity to CMV and involve receptors belonging to the Killer-cell Immunoglobulin-like Receptor (KIR) and CD94-NKG2 families. The CD94-NKG2 receptors consist of an invariant CD94 subunit covalently associated with a member of the NKG2 family, predominately NKG2A/B (2A, inhibitory) or NKG2C (2C, activating). Following CMV infection in healthy donors, there is an expansion of NK cells expressing activating 2C receptors, which are typically characterised by increased cytolytic activity, indicating an important mechanism for the control of the virus. Whether an expansion of 2C+ NK cells occurs in lung transplant recipients following CMV infection, and whether such cells can contribute to viral control, remains unclear. Here, we longitudinally assessed the changes in 2C+ NK cells in the blood and bronchoalveolar lavage (BAL) of lung transplant recipients, with a particular focus on individuals who were CMV naïve at the time of transplant and received a CMV+ allograft. We observed the expansion of 2C+ NK cells in the blood of these patients co-incident with the detection of CMV reactivation in the lung allograft. Moreover, 2C+ NK cells were enriched in the BAL of these recipients and expressed distinct KIR subsets. Monitoring the expansion of NK cell subsets post lung transplant may be a useful biomarker for assessing patient levels of CMV immunity.