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Mechanisms of Long-Term Donor-Specific Allograft Survival Induced
by Pretransplant Infusion of Lymphocytes
Liming Yang,
Barb Du Temple,
Qasim Khan, and
Li Zhang
From the Department of Cellular and Molecular Pathology, Multi Organ
Transplantation Program, The Toronto Hospital Research Institute,
University of Toronto, Toronto, Canada.
Pretransplantation donor-specific transfusion (DST) can enhance
allograft survival in man and animals. However, due to the lack of a
specific marker to identify donor-reactive cells in vivo in man and
normal (nontransgenic) animals, the underlying mechanism remains
unknown. In this study, we use 2CF1 transgenic mice
expressing a transgenic T-cell receptor (TCR) specifically recognizing
Ld, a major histocompatibility complex (MHC) class I
molecule, to delineate the role of DST in long-term skin allograft
survival and its underlying mechanisms. Our main findings include: (1) in the absence of any other immunosuppressive treatment, a single dose
pretransplantation infusion of viable splenocytes from an Ld+ donor is sufficient to induce permanent
donor-specific skin allograft survival in 2CF1
anti-Ld TCR transgenic mice; (2) DST leads to a
deletion of the majority (>60%) of donor-reactive T cells in the
periphery of the recipient. However, deletion does not necessarily
result in tolerance; (3) remaining donor-reactive T cells from
DST-treated mice are fully responsive to Ld in vitro, and
can suppress the antidonor response of naive T cells in vitro only when
exogenous interleukin (IL)-4 is provided; and (4) the sera level of
IL-4 in DST-treated tolerant mice is significantly increased. These
results suggest that the generation of a subset of T cells with the
potential to specifically inhibit antidonor responses, together with
promotion of IL-4 production in recipients, may be important mechanisms
for the induction and maintenance of antigen-specific tolerance.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 324-330
© 1998 by The American Society of Hematology.
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