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From the Laboratory of Immunology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts.
PURPOSE. To evaluate the differential gene expression of chemokines after corneal transplantation and to determine the chemokines associated with allograft rejection.
METHODS. Orthotopic mouse corneal transplantation was performed in two fully mismatched-strain combinations using C57BL/6 (H-2b) and BALB/c (H-2d) mice as recipients and BALB/c and C57BL/6 mice as donors. Normal nonsurgical eyes served as negative control specimens and syngeneic transplants (isografts) as control specimens for the alloimmune response. Chemokine gene expression in accepted and rejected allografts and appropriate control specimens was determined by a multiprobe RNase protection assay system.
RESULTS. In eyes with rejected allografts, there was overexpression of regulated
on activation normal T-cell expressed and secreted (RANTES), macrophage
inflammatory protein (MIP)-1
, MIP-1ß, MIP-2, and monocyte
chemotactic protein (MCP)-1 in both C57BL/6 and BALB/c recipients. In
addition, C57BL/6 eyes with rejected allografts expressed very high
levels of interferon-
–inducible protein of 10 kDa (IP-10) mRNA, in
contrast to BALB/c eyes with rejected allografts, in which IP-10
expression remained very low. In contrast, lymphotactin gene expression
increased only slightly in rejected allografts, and eotaxin mRNA, which
was also detected in normal eyes, remained unchanged among isograft and
allograft groups. T-cell activation gene (TCA)-3 mRNA was not detected
in any of the assayed eyes.
CONCLUSIONS. Increased expression of mRNA for select chemokines of the CXC () and
CC (ß) families is associated with corneal allograft rejection.
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 in alloimmune
reactivity observed among different murine
strains.
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