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 CDS' 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.