Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection.

Abstract

To determine the pattern of cellular expression of donor MHC class I and class II antigens during the course of rat cardiac allograft rejection, ACI cardiac allografts transplanted to BN recipients were examined from day 2 to day 6 using immunohistologic and immunoelectron microscopic methods. We used both monomorphic and donor-specific mouse anti-rat MHC class I and class II mAbs in this study. In normal ACI hearts, MHC class I reactivity was confined to the vascular endothelium and to interstitial cells. Ongoing rejection was characterized by an increased donor MHC class I staining intensity of microvascular endothelium and induction of donor class I surface reactivity on cardiac myofibers. Donor MHC class II reactivity was exclusively confined to interstitial dendritic cells (IDC) in both normal ACI hearts and in rejecting allografts, although rejection was associated with marked fluctuations in class II IDC frequency. An early numerical depression in class II IDC present in both allografts and syngeneic heart grafts was attributed to a direct effect of the transplantation procedure. By days 3-4, allografts showed an absolute overall increase in donor class II IDC frequency, which was associated with the presence of multiple localized high-density IDC-lymphocyte aggregates. The lymphocytes present in the focal areas were predominantly of the class II-reactive Th cell subpopulation. These aggregates may thus represent the in vivo homologue of dendritic cell-lymphocyte clustering, which has been shown to be required for primary class II allosensitization in the rat and mouse in vitro. During the late phase of rejection, there was a marked numerical fall in donor class II IDC, which correlated with extensive overall graft destruction. This study has shown that acute rat cardiac allograft rejection can occur in the absence of donor MHC class II expression by allograft vascular endothelium and cardiac myofibers. The IDC, which are believed to represent the principal class II alloantigen presenting cells in the rat heart, remain the sole class II-expressing cellular constituents of the graft throughout the course of rejection.

Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues.

“…Thus migration of DC from the blood to the spleen is regulated by T cells. Although we initially thought that this might be due to direct DC-T cell clustering, analogous to that studied in vitro (30) and implicated in vivo (38), elsewhere we present evidence that is contrary to this idea (17). In particular, we have found that the DC are initially localized within the red pulp of the spleen but that later, and only after a period of what appears to be active migration, they enter the white pulp.…”

Donor and recipient leukocytes in organ allografts of recipients with variable donor-specific tolerance: With particular reference to chronic rejection

“…41 Consistent with such reports, B7 was expressed by donor but almost no recipient cells in the LEW heart allografts of the present study that had been transplanted to BN recipients who were immunologically defenseless because they had been pretolerized with an orthotopic LEW liver (group 6). The other way around, we 23 and others 42 have described antigraft host T cells assembled in rosettes around donor DCs in rejecting rat organ allografts, suggesting the local induction of an HVG response.…”

Different Qualitative and Quantitative Regulation of Vβ TCR Transcripts During Early Acute Allograft Rejection and Tolerance Induction

“…The idea that the T cells with altered CDR3 length distribution that accumulate in tolerated hearts are regulatory cells is an attractive possibility. Graft-resident dendritic cells, the only class II ϩ APC of normal rat hearts (39), are likely to be involved in this process, as they have been shown to be required in the graft for tolerance induction following DST (40). Alternatively, putative regulatory cells with strongly skewed V␤ usage may regulate the capacity of graft dendritic cells to stimulate naive T cells.…”