Elevated CD56^dimCD16^neg NK Cells on Day 28 after HCT: Role in Immunity Against Viral Infections or Residual Tumor Cells?.

Natural killer (NK) cells represent a lymphocyte subset important in the immune surveillance against virus infected and malignant cells. In humans, two major NK cell subsets have been defined by CD56 and CD16 staining:

1. Regulatory NK cells (CD56 ^high CD16 ^neg), which are potent cytokine (IFNg) producers; and

2. Cytolytic NK cells (CD56 ^dim CD16 ^pos) that are involved in target cell lysis.

Functions of other NK cell subset are unknown. One of such subset, CD56 ^dimCD16 ^neg NK cells have recently been reported to represent cytolytic cells, degranulated after contact with target cells. NK cells are the first lymphocyte subset recovering to normal quantity and function after an allogeneic or autologous HCT, typically by 4 weeks post HCT. In the present investigation, we attempted to determine percentages of following NK cell subsets (Regulatory NK cells, Cytolytic NK cells, CD56^dimCD16 ^neg, CD56 ^highCD16 ^pos and CD56^neg CD16 ^high NK cells) at multiple time points (day 28, 56, 84, 180 and 365) after allogeneic (n= 32) and autologous (n= 25) HCT and compared with that of healthy individuals (n=14). Whole blood specimen was incubated with fluorochrome-conjugated monoclonal antibodies (CD3-ECD, CD14-PE, CD56-FITC and CD16-PC5) and analyzed by four color flowcytometry. NK cells were defined as mononuclear cells expressing CD16 or CD56 and not expressing CD3 or CD14. The most striking finding was that of significant increase in percentage of CD56^dimCD16^−ve cells (among NK cells) on day 28. This was true for both autologous HCT recipient (n=24; median = 1.02% of total NK cells) and allogeneic HCT recipient (n=26; median = 1.1% of total NK cells) in comparison to the healthy individuals (n=14; median = 0.56% of total NK cells). We speculate the rise in CD56^dimCD16^−ve NK cells at 1 month post HCT may be due to increased degranulation of cytolytic NK cells in response to viral infections or residual malignancy.