Differential chemokine gene expression in corneal transplant rejection

PURPOSE. To evaluate the differential gene expression of chemokines after c orneal transplantation and to determine the chemokines associated with allo graft rejection. METHODS. Orthotopic mouse corneal transplantation was performed in two full y mismatched-strain combinations using C57BL/6 (H-2(b)) and BALB/c (H-2(d)) mice as recipients and BALB/c and C57BL/6 mice as donors. Normal nonsurgic al eyes sen ed as negative control specimens and syngeneic transplants (iso grafts) as control specimens for the;alloimmune response. Chemokine gene ex pression in accepted and rejected allografts and appropriate control specim ens was determined by a multiprobe RNase protection assay system. RESULTS. In eyes with rejected allografts, there was overexpression of regu lated on activation normal T-cell expressed and secreted (RANTES), macropha ge inflammatory protein (MIP)-1 alpha MIP-1 beta, MIP-2, and monocyte chemo tactic protein (MCP)-1 in both C57BL/6 and BALB/c recipients. In addition, C57BL/6 eyes with rejected allografts expressed very high levels of interfe ron-gamma-inducible protein of 10 kDa (IP-10) mRNA. in contrast to BALB/c e yes with rejected allografts, in which IP-10 expression remained very low. In contrast, lymphotactin gene expression increased only slightly in reject ed allografts, and eotaxin mRNA, which was also detected in normal eyes, re mained unchanged among isograft and allograft groups. T-cell activation gen e (TCA)-3 mRNA was not detected in any of the assayed eyes. CONCLUSIONS. Increased expression of mRNA fur select chemokines of the CXC (alpha) and CC (beta) families is associated with corneal allograft rejecti on. Significantly elevated IP-10 gene expression in high-rejector C57BL/6, but not in low-rejector BALB/c, hosts suggests that differential activation of chemokines may be related to differences ill alloimmune reactivity obse rved among different murine strains.