title: Recovery of CMV-specific CD8+ T cells and Tregs after allogeneic peripheral blood stem cell transplantation.
abstract: Recovery of cytomegalovirus (CMV)-specific CD8+ T cells after allogeneic stem cell transplantation (SCT) is critical for protection against CMV infection and disease. Moreover, Foxp3+CD4+CD25(high) regulatory T cells (Tregs) are a major regulator of adaptive immunity, preventing graft-versus-host disease (GVHD) and so promoting timely and complete immune recovery. The aim of our study was to evaluate the recovery of circulating tetramer-based CMV-specific CD8+ T cells and T regs in 46 patients after allogeneic peripheral blood SCT (PBSCT). CMV infection and/or disease was observed in 7% and 94% of patients with or without CMV-specific CD8+ T cells recovery (P < .001), and in 77% and 4% of patients with or without acute GVHD (aGVHD) (P < .001), respectively. T regs values were higher in patients without than with CMV infection and/or disease at 2 (P < .001) and 3 months (P < .001) after allogeneic PBSCT, respectively. Moreover, we observed a positive correlation between T regs and the recovery of CMV-specific CD8+ T cells at 2 (r = .61, P < .0001) and 3 (r = .72, P < .00001) months, respectively. Tregs were higher in patients without than with aGVHD at 1, 2 (P < .001) and 3 months (P < .0001), respectively. At multivariate logistic regression, aGVHD (odds ratio [OR]: 2.60, 95% confidence interval [CI] [1.3-5.0], P = .0006) and CMV-specific CD8+ T cells recovery (OR:2.25, 95% CI [1.2-4.8], P = .05) were correlated with CMV infection and/or disease, whereas no correlation was found for Tregs, absolute neutrophil count, patients' and donors' age, disease status pretransplantation, type of disease, and CMV serology. Taken together, our data may suggest the existence of a correlation between Tregs and the recovery of CMV-specific CD8+ T cells; Tregs may preserve an optimal microenvironment for the reconstitution of functional immunity and mediate protective effects against aGVHD.
authors.affiliation: Hematology Section, Department of Pathology and Hematology, University of Bari, Piazza Giulio Cesare 11, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Pastore
authors.forename: Mario
authors.initials: M
authors.lastname: Delia
authors.forename: Anna
authors.initials: A
authors.lastname: Mestice
authors.forename: Tommasina
authors.initials: T
authors.lastname: Perrone
authors.forename: Paola
authors.initials: P
authors.lastname: Carluccio
authors.forename: Francesco
authors.initials: F
authors.lastname: Gaudio
authors.forename: Annamaria
authors.initials: A
authors.lastname: Giordano
authors.forename: Antonella Russo
authors.initials: AR
authors.lastname: Rossi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ricco
authors.forename: Manuela
authors.initials: M
authors.lastname: Leo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Liso
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000209:etiology / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology / Q000821:virology; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D020127:Recovery of Function; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous