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Background: Although graft resident, bone
marrow-derived antigen presenting cells (APCs) are highly immunogenic,
they are not required for rejection, as chimeric BALB/c hearts bearing CBA
APCs are rejected by CBA recipients, despite a modest prolongation in
survival. The goal of this study was to characterize the cellular
infiltrate in acutely rejecting chimeric BALB/c hearts to determine the
allorecognition pathway(s) responsible.
Methods:
Chimeric BALB/c hearts were created via CBA->BALB/c bone marrow
transplantation. Control or chimeric hearts were transplanted
heterotopically into naive CBA recipients. Immunohistochemisty (IHC) was
performed using a standard avidin biotin complex immunoperoxidase
technique on frozen sections obtained from rejected hearts. Antibodies
against CD4, CD8, CD11b (macrophages[Mo]), CD11c (dendritic cells[DC]) and
CD45R/B220 (B cells) were used. One frozen section from each case was
stained with hematoxylin and eosin to grade the rejection.
Results:
As in previous studies, APC replacement prolonged graft survival, but did
not prevent rejection. All specimens showed acute cellular rejection
with no difference in ISHLT grade between groups. Cellular infiltrates in both groups were predominantly effector CD8+ T cells and CD11b+Mo. Chimeric hearts showed an increase in CD11c+ let DC and CD45R/B220+ B cells and CD4+T cells (p=.01, .03, and .05 respectively, Mann-Whitney U Test).
Conclusion: Chimeric hearts showed a different pattern of cellular rejection with increased numbers of recipient-type APCs (both B cells and DC) and CD4+ T cells. This supports the hypothesis that heart depleted of donor-type APCs are rejected by the indirect allorecognition pathway.