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Phenotypic and Functional Characteristics of NK Cells Associated with Cytomegalovirus (CMV) Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

Track: Poster Abstracts
Wednesday, February 26, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Ryotaro Nakamura, MD , Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
Anne Franck , Department of Virology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, Duarte, CA
Ghislaine Gallez-hawkins , Department of Virology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
Laetitia Jeannet , Department of Virology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, Duarte, CA
Xiuli Li , Department of Virology, City of Hope, Duarte, CA
Stephen J. Forman, MD , Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, CA
John A. Zaia, MD , Virology, Beckman Research Institute of City of Hope, Duarte, CA
Cytomegalovirus (CMV) infection represents a major complication in hematopoietic stem cell transplantation (HCT). There is accumulating evidence that immune responses to CMV infection involve the expansion of specific subsets of NK cells largely driven by the activating receptor NKG2C.

Under an IRB approved protocol (COH 09038), we prospectively examined the reconstitution of NK cells post-HCT (days 21, 30, 45, 80 and 120) with regards to their immunophenotypes and functions. A total of 111 patients are enrolled (median age: 54, range 19-70) who underwent HCT from related (n=49) or unrelated donors (n=62) after either fully ablative (n=36) or reduced-intensity (n=75) conditioning. Donor (D)/Recipient (R) serostatus was D+/R+ in 69, D-/R+ in 33, and D+/R- in 6 pairs. Acute GVHD grade II-IV was observed in 49 patients (47%). CMV reactivations were seen in 26 patients (23.4%) with the median time of reactivation on day 49, including 2 cases of CMV disease.  

CMV reactivation was significantly associated with increased %NK cells expressing PD-1, IFN-gamma, perforin, and granzyme B (Table 1). More focused analysis on available day 80 samples (n=75) demonstrated a significant increase in NK cells expressing NKG2C in patients with CMV reactivations (24.2%, n=17) compared with no reactivations (13.2%, n=58, p=0.018), consistent with published reports. Among NKG2C+NKcells, CMV reactivation was associated with increased granzyme B (85.4% vs. 56.9%, p=0.003) and Ki67 expression (7.0% vs. 2.9%, p=0.03).

We further explored NK responses to CMV antigen by co-culturing PBMC (day 80 samples) and pp65 peptide mix for 24 hours. There was no significant change in %NKG2C+NK cells before and after pp65 stimulation. Interestingly, NKG2C-NK cells showed a response to pp65 stimulation in their expression of CD137 (pre: 0.06% vs. post: 0.23%, p=0.005) and IFN-gamma (pre: 1.6% vs. post: 2.1%, p=0.03 in CMV reactivators), suggesting a potential role of NKG2C-NK cells in CMV infections.

In summary, our data support that CMV reactivation is associated with expansion (Ki67) and cytotoxic functions (perforin, granzyme, IFN-gamma) of NK cells expressing NKG2C following allogeneic HCT.

Disclosures:
Nothing To Disclose
See more of: Poster Session 1: Immune Reconstitution
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