Background. Based on their chemoattractant properties, it is likely that ch
emokines play a role in recruiting alloantigen-primed T cells to allografts
and in amplifying inflammation within the graft, The graft-infiltrating le
ukocytes producing specific chemokines remain largely unknown,
Methods. We tested the intragraft RNA expression of the chemokine RANTES (r
egulated on activation normal T expressed and secreted) and granzyme B duri
ng rejection of full thickness, allogeneic skin grafts by C57BL/6 mice. Gra
fts 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 g
raft sections to test colocalization of RANTES protein and graft-infiltrati
ng 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 o
bserved 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 pr
otein was associated with a small number of graft-infiltrating CDS' T cells
but was also associated with endothelial cells and with many graft-infiltr
ating CD4(+) T cells.
Conclusions. CD8(+) T cells produce RANTES during allogeneic skin graft rej
ection. In the allograft, the chemokine also colocalizes with CD4(+) T cell
s that do not produce RANTES.