Recovery of CMV-specific CD8+ T cells and Tregs after allogeneic peripheral blood stem cell transplantation.
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.
Pastore
Domenico
D
Hematology Section, Department of Pathology and Hematology, University of Bari, Piazza Giulio Cesare 11, Bari, Italy.
Delia
Mario
M
Mestice
Anna
A
Perrone
Tommasina
T
Carluccio
Paola
P
Gaudio
Francesco
F
Giordano
Annamaria
A
Rossi
Antonella Russo
AR
Ricco
Alessandra
A
Leo
Manuela
M
Liso
Vincenzo
V
Specchia
Giorgina
G
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