Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4(+)CD25(high) regulatory T cells (T(regs)) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4(+)CD25(high) T(regs) in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of T(regs) in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the T(regs) purified from SCT patients exhibited a more potent suppressive activity than T(regs) isolated from healthy volunteers. Patients in whom T(regs) numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in T(regs) might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that T(regs) exert an inhibitory effect on GvL.
Nadal
E
E
Department of Haematology, Hammersmith Hospital, Imperial College London, London, UK.
Garin
M
M
Kaeda
J
J
Apperley
J
J
Lechler
R
R
Dazzi
F
F
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000276:immunology*
D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D016044:Fusion Proteins, bcr-abl