Appearance of cytomegalovirus-specific T-cells predicts fast resolution of viremia post hematopoietic stem cell transplantation.
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.
['Pelák|Ondřej|O|', 'Stuchlý|Jan|J|', 'Król|Ladislav|L|', 'Hubáček|Petr|P|', 'Keslová|Petra|P|', 'Sedláček|Petr|P|', 'Formánková|Renata|R|', 'Starý|Jan|J|', 'Hrušák|Ondřej|O|', 'Kalina|Tomáš|T|']
D000293:Adolescent D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D002648:Child D002675:Child, Preschool D003587:Cytomegalovirus D003586:Cytomegalovirus Infections D005260:Female D005434:Flow Cytometry D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D007223:Infant D008297:Male D016176:T-Lymphocyte Subsets D014766:Viremia D055815:Young Adult
T-cells cytomegalovirus flow cytometry bone marrow transplantation immune reconstitution