Appearance of cytomegalovirus‐specific T‐cells predicts fast resolution of viremia post hematopoietic stem cell transplantation

• Published in: Cytometry. Part B, Clinical cytometry Clinical cytometry, 2017-09, Vol.92 (5), p.380-388
• Main Authors: Pelák, Ondřej, Stuchlý, Jan, Król, Ladislav, Hubáček, Petr, Keslová, Petra, Sedláček, Petr, Formánková, Renata, Starý, Jan, Hrušák, Ondřej, Kalina, Tomáš
• Format: Article
• Language: English
• Subjects: Activation; Adolescent; bone marrow transplantation; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; CD40L protein; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; Child; Child, Preschool; Combinatorial analysis; Confidence intervals; Cytomegalovirus; Cytomegalovirus - metabolism; Cytomegalovirus Infections - virology; Cytometry; Degranulation; Female; Flow cytometry; Flow Cytometry - methods; Hematopoietic Stem Cell Transplantation - methods; Humans; immune reconstitution; Infant; Interferon; Interleukin 2; Lymphocytes; Lymphocytes T; Male; Patients; Risk; Stem cell transplantation; Stem cells; T-Lymphocyte Subsets - immunology; Transplantation; T‐cells; Viremia; Viremia - metabolism; Young Adult
• ISSN: 1552-4949; 1552-4957
• DOI: 10.1002/cyto.b.21348

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