Patterns of cytomegalovirus reactivation are associated with distinct evolutive profiles of immune reconstitution after allogeneic hematopoietic stem cell transplantation.
T cell-mediated immunity is essential for the control of cytomegalovirus (CMV) infections in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify patterns of CMV-specific immune responses associated with multiple or prolonged reactivations. We analyzed findings in 116 recipients during the course of infection or reactivation and latency. CD8(+) T cell responses were determined weekly, using HLA class I tetramers together with extended phenotypic analyses. Our results confirmed that recipients of allo-HSCT from unrelated donors were more susceptible to multiple reactivations and that the donor's CMV serological status influenced the occurrence of prolonged reactivations. We found that a lack of CMV-specific T cells after the first episode of reactivation was associated with multiple subsequent reactivations. In patients with uncontrolled reactivations, CMV-specific T cells of the late differentiation phenotype CD45RA(+)CD27(-)CD28(-) did not develop. Longitudinal evaluation of CD27 and CD45RA expression within the tetramer-positive subset could help identify patients in whom a protective immune response is developing. Evaluation of CMV-specific immune responses during the first episode of reactivation, together with extended phenotypes, could thus improve immune monitoring, especially in recipients at risk of uncontrolled viral reactivation.
Moins-Teisserenc
Hélène
H
Laboratoire d'Immunologie et d'Histocompatibilité, Centre d'Investigations Biomédicales Hématologie-Oncologie-Greffes, Paris, France. helene.moins@univ-paris-diderot.fr
Busson
Marc
M
Scieux
Catherine
C
Bajzik
Véronique
V
Cayuela
Jean-Michel
JM
Clave
Emmanuel
E
de Latour
Régis Peffault
RP
Agbalika
Félix
F
Ribaud
Patricia
P
Robin
Marie
M
Rocha
Vanderson
V
Gluckman
Eliane
E
Charron
Dominique
D
Socié
Gérard
G
Toubert
Antoine
A
D015703:Antigens, CD / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics; D010641:Phenotype; D012008:Recurrence; D012307:Risk Factors; D014019:Tissue Donors / Q000706:statistics & numerical data; D014184:Transplantation, Homologous; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics; D014775:Virus Activation; D017735:Virus Latency
D015703:Antigens, CD; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens