Cellular basis of skin allograft rejection in mice: specific lysis of allogeneic skin components by non-T cells.

BACKGROUND

It has been generally assumed that CD8+ T cells mediate direct lysis of allografts and that their growth, differentiation, and activation are dependent upon cytokine production by CD4+ T cells. However, both the generation of CD4- or CD8-deficient mice and adoptive transfer experiments with CD4+ T cells from CD8-deficient mice demonstrate that noncytotoxic CD4+ T cells alone are sufficient to induce skin or organ allograft rejection. Furthermore, we have reported that the major effector cells responsible for allografted-tumor (e.g., Meth A) rejection are allograft-induced macrophages (AIM) with MHC haplotype specificity.

METHODS

We characterized the macrophages migrating into the rejection site of allografted skin by immunohistochemical and in situ hybridization analyses using an antibody (K16.5) specific for AIM and a cDNA (pK30) encoding the antigen. To determine the in situ effector cells responsible for the rejection, we prepared both effector cells and target cells from the graft-graft bed border.

RESULTS

The macrophages seemed to be morphologically (monocytic), phenotypically (K16.5+/pK30+), and functionally (cytotoxic against Meth A cells) AIM. The AIM population in bulk infiltrates taken from the rejection site was cytotoxic against allografted, but not self, skin components (e.g., fibroblasts, myocytes, endothelial cells, and epithelial cells). In contrast, other types of infiltrating cells including lymphocytes and granulocytes were virtually inactive toward these targets, and NK-1.1+ cells hardly infiltrated into the rejection site.

CONCLUSIONS

These data suggest that the major effector cells mediating allografted skin rejection are AIM and not T cells.