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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4539-4544
RAPID COMMUNICATION
Critical Requirement for Graft Passenger Leukocytes in Allograft
Tolerance Induced by Donor Blood Transfusion
Régis Josien,
Michèle Heslan,
Sophie Brouard,
Jean-Paul Soulillou, and
Maria-Cristina Cuturi
From the INSERM Unit 437 and ITERT "Institut de Transplantation et
de Recherche en Transplantation," Immeuble Jean Monnet, Nantes,
France.
Tolerance to a vascularized allograft can be induced in adult
animals by pregraft donor-specific blood transfusion (DST). Mechanisms
underlying this effect appear to depend on unresponsiveness of
alloreactive T-helper cells. In this study, we examined the roles of
DST and cellular components of the allograft that are important in
inducing T-cell unresponsiveness in a rat model. DST alone did not
tolerize alloreactive recipient T-helper cells, but the combination of
DST and heart allograft induced profound inhibition of the antidonor
proliferative response in spleen but not in lymph node cells. When
heart allografts were depleted of passenger leukocytes by pretreating
the donor with cyclophosphamide or by parking the graft for 2 months in
a tolerant recipient, tolerance induction in DST-treated recipients was
abrogated. Tolerance could then be restored in a majority of
DST-treated recipients of passenger leukocytes depleted grafts by
injecting them at the time of grafting with donor, but not third-party,
dendritic cells. This indicates that graft passenger leukocytes, most
likely dendritic cells, are required for DST-induced allograft
tolerance.
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