Pretransplantation CMV-specific T cells protect recipients of T-cell-depleted grafts against CMV-related complications

被引:44
作者
Chalandon, Y
Degermann, S
Villard, J
Arlettaz, L
Kaiser, L
Vischer, S
Walter, S
Heemskerk, MHM
van Lier, RAW
Helg, C
Chapuis, B
Roosnek, E
机构
[1] Univ Geneva, Hop Cantonal, Div Hematol, Unite Immunol Transplantat, CH-1211 Geneva, Switzerland
[2] Univ Geneva, Hop Cantonal, Div Immunol & Allergol, CH-1211 Geneva, Switzerland
[3] Univ Geneva, Hop Cantonal, Dept Internal Med, Div Infect Dis,Cent Lab Virol, CH-1211 Geneva, Switzerland
[4] Univ Tubingen, Inst Cell Biol, Dept Immunol, Tubingen, Germany
[5] Leiden Univ, Ctr Med, Dept Hematol, Leiden, Netherlands
[6] Univ Amsterdam, Acad Med Ctr, Expt Immunol Lab, NL-1105 AZ Amsterdam, Netherlands
关键词
D O I
10.1182/blood-2005-07-2746
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have studied cytomegalovirus (CMV) immunity in 17 CMV-positive recipients of T-cell-depleted or T-cell-replete grafts. In recipients of T-cell-replete grafts, the patient's CMV-specific T-cell response was completely ablated. Because primary anti-CMV responses were rare during the first year, immunity depended essentially on the transfer of donor CMV-specific T cells and, therefore, on the CMV positivity of the donor. In the recipients of T-cell-depleted grafts, CMV-specific cytotoxic T cells were of recipient origin in 2 patients who underwent transplantation with CMV-negative donors and in 3 of 8 patients who underwent transplantation with CMV-positive donors, and they were of mixed or donor origin in the other 5 patients studied. Recipient CMV-specific T cells responded vigorously to antigen ex vivo and persisted for several years without replenishment by donor cells. Furthermore, they appeared to have a protective effect because CMV-related complications were absent in the patients with CMV-specific T cells of recipient origin. Clinical outcomes of a cohort of 91 patients corroborated the experimental results. Patients with recipient T cells in their blood were protected regardless of the donor immune status. Hence, when a T-cell depletion protocol is used that favors the survival of recipient T cells, the patient's pretransplantation CMV-specific immunity protects against posttransplantation CMV-related complications.
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收藏
页码:389 / 396
页数:8
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