Appearance of cytomegalovirus‐specific T‐cells predicts fast resolution of viremia post hematopoietic stem cell transplantation. Issue 5 (12th January 2016)

• Record Type: Journal Article
• Authors: Pelák, Ondřej; Stuchlý, Jan; Król, Ladislav; Hubáček, Petr; Keslová, Petra; Sedláček, Petr; Formánková, Renata; Starý, Jan; Hrušák, Ondřej; Kalina, Tomáš
• Is Part Of: Cytometry. Volume 92:Issue 5(2017)
• Page Start: 380
• Page End: 388
• Publication Date: 2016-01-12
• Subjects: cytomegalovirus -- bone marrow transplantation -- T‐cells -- immune reconstitution -- flow cytometry; Flow cytometry -- Diagnostic use -- Periodicals; Cytodiagnosis -- Periodicals; 616.07582
• DOI: 10.1002/cyto.b.21348
• Languages: English
• ISSNs: 1552-4949

Abstract

Abstract : Background: Cytomegalovirus (CMV) specific T‐cells are known to provide long‐term control of CMV reactivation, which is a frequent complication of hematopoietic stem cell transplantation. We have studied 58 pediatric patients after hematopoietic stem cell transplantation who suffered from CMV reactivation to reveal which functional T cell subset is best correlating with successful reactivation resolution and which protects from reactivation episode. Methods: Detection of 30 combinatorial subsets of four types of response to ex vivo CMV stimulation (IFNγ secretion, IL‐2 secretion, CD40L upregulation and degranulation) that were detectable on either CD8+ or CD4+ T cells through flow cytometry intracellular cytokine staining was used. Results: We found that the presence of CD8+ dual positive (IFNγ+ and IL‐2+) cells is the most accurate functional parameter that can predict fast resolution of CMV reactivation. Next, we show that the presence of CD8+ dual positive (IFNγ+ and IL‐2+) and CD8+ IFNγ+ cells provides a protective effect (a hazard risk of 0.28 (confidence interval 0.18 – 0.43) and 0.45 (CI 0.27 – 0.75), respectively) and the presence of corticotherapy increases the risk of reactivation (HR 2.47 (CI 1.82‐3.36)). Thus, a patient without corticotherapy and with both of the critical T cell subsets present has a cumulative 19.6 times lower risk of developing CMV reactivation than a patient on corticotherapy and without CD8+ dual positive (IFNγ+ and IL‐2+) or CD8+ IFNγ+ cells. Conclusions: We have established parameters of CMV specific functional response ex vivo that can be used in assisting clinical management of patients with CMV reactivation. © 2015 International Clinical Cytometry Society