Pretransplantation CMV-specific T cells protect recipients of T-cell-depleted grafts against CMV-related complications.
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.
Chalandon
Yves
Y
Division of Hematology, Department of Internal Medicine, University Hospital Geneva, Switzerland.
Degermann
Sylvie
S
Villard
Jean
J
Arlettaz
Lionel
L
Kaiser
Laurent
L
Vischer
Solange
S
Walter
Steffen
S
Heemskerk
Mirjam H M
MH
van Lier
Rene A W
RA
Helg
Claudine
C
Chapuis
Bernard
B
Roosnek
Eddy
E
D000328:Adult; D000818:Animals; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007109:Immunity; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion / Q000379:methods*; D051379:Mice; D008875:Middle Aged; D012189:Retrospective Studies; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D016896:Treatment Outcome