Introduction: Active CMV infection is known to be associated with risk for ABMR in allograft recipients. Ab-dependent cellular cytotoxicity (ADCC) primarily mediated by NK cells via CD16 is critical for elimination of CMV infected cells. Recent study showed that G2C+CD57+ cells expanded by CMV infection are highly responsive to CMV-Ab-dependent stimulation via CD16 signaling. Here, we examine if G2C+57+ cells are also highly responsive to allo-Ab-mediated NK cell stimulation by IFNg flow cytometry (CFC), to explore the possibility that CMV infection increases sensitivity of NK cells for alloantigen targets, increasing risk for ABMR.

Methods: Blood from 11 CMV sero+ and 10 sero- individuals were stained with Abs to CD3, CD4, CD16, CD56, CD57, CD107A and NKG2C. CMV-Ab or allo-Ab-mediated NK cell response were measured by incubating whole blood w/ CMV lysate or leukocytes w/ allo-Ab-coated irradiated PBMC, respectively, followed by IFNg-CFC.

Results: Total CD56+ NK cell% in lymphocytes were similar in CMV sero+ & – blood (12±6% v. 12±7%) and most NK cells were CD16+ (91±7% v. 87±8%). Among CD56+ NK cell subsets subdivided by G2C/57 positivity (G2C-57+, G2C+57+, G2C-57- & G2C+57-), significantly higher G2C+57+ cell% (p<0.05) was observed in sero+ blood and was the major difference between sero+ (35±14%, 24±8%, 33±11% & 8±5%, respectively) and sero- blood (36±13, 3±2, 53±12 & 8±6). In the CMV-Ab-CFC, significantly higher IFNg+ or CD107a+CD56+ NK cells were detected in CMV-lysate-stimulated sero+ compared to sero- blood (IFNg: 26±67% v. 0±1%; CD107a: 23±8% v. 0±1%: both p<0.05). Of importance, G2C+57+ cells showed the highest responses although the other 3 subsets responded as well. In the allo-Ab-CFC, G2C+57+ cells from sero+ blood showed the highest response, while we saw minimal or no responses in G2C+57+ cells from sero- blood despite similar CD16 expression (IFNg: 36±24% v. 6±5%; CD107a: 28±17% v. 3±2%: both p<0.05).

Conclusion: G2C+57+ NK cell are selectively activated in response to CMVantigens. The same is true for G2C+57+ cell response to allo-Ab-mediated NK stimulation. This study suggests that G2C+57+ cells may be primarily responsible for ADCC responses to allo-antigens in mediation of ABMR in CMV sero+ HS pts.

CITATION INFORMATION: Shin B., Puliyanda D., Pizzo H., Jordan S., Toyoda M. NKG2C+CD57+ NK (G2C+57+) Cells Expanded by CMV Infection Are Highly Responsive to Allo-Antibody (Ab)-Mediated NK Cell Stimulation Am J Transplant. 2017;17 (suppl 3).

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