CD8+ T cells produce RANTES during acute rejection of murine allogeneic skin grafts.

BACKGROUND

Based on their chemoattractant properties, it is likely that chemokines play a role in recruiting alloantigen-primed T cells to allografts and in amplifying inflammation within the graft. The graft-infiltrating leukocytes producing specific chemokines remain largely unknown.

METHODS

We tested the intragraft RNA expression of the chemokine RANTES (regulated on activation normal T expressed and secreted) and granzyme B during rejection of full thickness, allogeneic skin grafts by C57BL/6 mice. Grafts with different immunogenetic disparities were chosen to test expression when rejection was mediated by CD4+, CD8+, or both CD4+ and CD8+ T cells. RNA expression was also tested in purified CD4+ and CD8+ T cell populations from skin graft recipients. Immunohistology was performed on graft sections to test colocalization of RANTES protein and graft-infiltrating CD4+ and CD8+ T cells.

RESULTS

Intra-allograft RANTES RNA expression was not observed during CD4+ T cell-mediated rejection. Expression of RANTES and granzyme B RNA was observed at low levels in purified populations of CD8+, but not CD4+, T cells from the spleen and lymph nodes of graft recipients beginning at day 7 after transplantation and increased thereafter. Intra-allograft RANTES protein was associated with a small number of graft-infiltrating CD8+ T cells but was also associated with endothelial cells and with many graft-infiltrating CD4+ T cells.

CONCLUSIONS

CD8+ T cells produce RANTES during allogeneic skin graft rejection. In the allograft, the chemokine also colocalizes with CD4+ T cells that do not produce RANTES.