title: CD3+/Tregs ratio in donor grafts is linked to acute graft-versus-host disease and immunologic recovery after allogeneic peripheral blood stem cell transplantation.
abstract: Graft-versus-host disease (GVHD), mediated by mature T cells present in the donor graft, remains a major complication after allogeneic peripheral blood stem cell transplantation (PBSCT). Regulatory T cells (Tregs) (CD4(+)CD25(high)Foxp3(+)) are believed to maintain tolerance and to inhibit GVHD after allogeneic PBSCT (allo-PBSCT). In this study, we analyzed the graft CD3(+)/Tregs ratio (gCD3/Tregs R) and evaluated its impact on acute GVHD (aGVHD) and immunologic recovery after myeloablative allo-PBSCT. We analyzed 65 consecutive patients who underwent transplantation with unmanipulated peripheral blood stem cells from an HLA-identical related donor (n = 45) or an HLA-identical unrelated donor (n = 20). The median CD3(+) and Tregs doses administered were 256 × 10(6)/kg of body weight (range, 67-550 × 10(6)/kg) and 12 × 10(6)/kg (range, 2-21 × 10(6)/kg), respectively; the median gCD3/Tregs R value was 18 (range, 8-250). Patients were subdivided into a high gCD3/Tregs R (≥36) group (HR; n = 26) and a low gCD3/Tregs R (<36) group (LR; n = 39). The incidence of aGVHD (grade II-IV) was lower in the LR group compared with the HR group (8/39 [20%] versus 22/26 [84%]; P < .001). Median cytomegalovirus-specific CD8(+) T lymphocytes were significantly higher in the LR group than in the HR group at 1 month (2 cells/μL versus 0 cells/μL; P < .001), 2 months (6 cells/μL versus 1 cell/μL; P < .001), and 3 months (15 cells/μL versus 3 cells/μL; P < .001) months. Moreover, cytomegalovirus infection/disease was observed in 15% of patients in the LR group versus 69% of patients in the HR group (P < .001). At multivariate logistic regression, gCD3/Tregs R was correlated both with aGVHD (odds ratio, 2.50; 95% confidence interval, 1.30-4.50; P = .05) and with cytomegalovirus infection/disease (odds ratio, 2.35; 95% confidence interval, 0.9-5.00; P = .05). Taken together, our data may suggest that the balance in favor of graft Tregs content is able to mediate protective effects against aGVHD and to maintain an optimal microenviroment for the reconstitution of functional immunity.
authors: Hematology Section, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors: Domenico
authors: D
authors: Pastore
authors: Mario
authors: M
authors: Delia
authors: Anna
authors: A
authors: Mestice
authors: Paola
authors: P
authors: Carluccio
authors: Tommasina
authors: T
authors: Perrone
authors: Francesco
authors: F
authors: Gaudio
authors: Paola
authors: P
authors: Curci
authors: Antonella Russo
authors: AR
authors: Rossi
authors: Alessandra
authors: A
authors: Ricco
authors: Giorgina
authors: G
authors: Specchia
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D017252:CD3 Complex / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D020127:Recovery of Function; D012189:Retrospective Studies; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D017252:CD3 Complex; D006680:HLA Antigens