Induction of chemokine gene expression during allogeneic skin graft rejection.
The factors mediating trafficking of alloantigen-primed T cells and mononuclear phagocytes to the site of an allograft during the graft rejection process remain largely undefined. Based upon their demonstrated chemoattractant properties, chemokines may play a role in directing inflammatory cells to graft sites and initiate rejection. To begin to investigate the role of chemokines in graft rejection, we used Northern blot analysis to examine the temporal expression of 6 chemokine genes in murine allogeneic skin grafts disparate at the entire MHC and minor antigens and grafts with a disparity at either single class I or class II MHC determinants. Two general patterns of chemokine gene expression in each of the allografts were observed. Intragraft expression of 1 group of chemokine genes, including macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, JE, and KC was observed at peak levels 3 days posttransplant in each of the 3 different allograft models. Expression of these genes in control isografts was at low levels, with the exception of JE, which was expressed at equivalent levels in all iso- and allografts for the first 4-5 days posttransplant, and KC, which was expressed at equivalent levels in C57BL/6 isografts and bm1 and bm12 allografts. A second group of chemokine genes, including RANTES (regulated upon activation normal T cell expressed and secreted) and IP-10 (interferon-gamma inducible protein), was expressed at low levels at early times after transplantation but at high levels 3-4 days before rejection of the allografts was complete. Isograft expression of RANTES and IP-10 was undetectable at the late time points. The results suggest that these 2 patterns of chemoattractant cytokine gene expression may be representative of the early inflammatory and the late T cell-mediated phases of the allograft rejection process, respectively.