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,
Departments of
*
Surgery and
Pathology, University of Wisconsin, Madison, WI 53792; and
Pathology and Laboratory Medicine Service, William S. Middleton Veterans Affairs Hospital, Madison, WI 53792
The recognition of allo-MHC and associated peptides on the surface
of graft-derived APC by host T cells (direct pathway allorecognition)
plays an important role in acute rejection after organ transplantation.
However, the status of the direct pathway T cells in stable long term
transplants remains unclear. To detect alloreactive T cell clones in
PBL and the allograft during the transplant tolerance, we utilized
RT-PCR instead of functional assays, which tend to underestimate their
in vivo frequencies. We established alloreactive CD4+ and
CD8+ T cell clones from peripheral blood sampled during the
stable tolerance phase of a patient whose graft maintained good
function for 9 years, 7 without immunosuppression. We analyzed the
sequence of TCR Vß and V
genes and made clonotype-specific probes
that allowed us to detect each clone in peripheral blood or biopsy
specimens obtained during a 1-year period before and after the rapid
onset of chronic rejection. We found an unexpectedly high level of
donor HLA-specific T cell clonotype mRNA in peripheral blood during the
late tolerance phase. Strong signals for two CD4+
clonotypes were detected in association with focal T cell infiltrates
in the biopsy. Chronic rejection was associated with a reduction in
direct pathway T cell clonotype mRNA in peripheral blood and the graft.
Our data are inconsistent with the hypothesis that direct pathway T
cells are involved only in early acute rejection events and suggest the
possibility that some such T cells may contribute to the maintenance of
peripheral tolerance to an allograft.
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