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.
Koga
S
S
Department of Urology, Cleveland Clinic Foundation, Ohio 44195, USA.
Novick
A C
AC
Toma
H
H
Fairchild
R L
RL
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D006084:Graft Rejection; D053804:Granzymes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
D018946:Chemokine CCL5; D012333:RNA, Messenger; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases