Abstract
Purpose: :
It has been widely accepted that Th1- and IFN-γ-mediated immune responses are indispensable for the corneal allograft rejection. However, C57BL/6-IFN-gamma knockout (GKO) mice rejected MHC-matched corneas that elicited intensive infiltration of macrophages and neutrophils, but no B cells and eosinophils. To evaluate the mechanism of neutrophils recruitment in GKO hosts, the gene expression of Th1-, Th2-, and TH17-type chemokines was investigated.
Methods: :
MHC-matched corneal grafts from 129 mice were placed in the eyes of wild-type (WT) C57BL/6 mice or GKO mice. Graft fates were assessed both clinically and histologically. At day 7 (before rejection period) and day 21 (at the time of the onset of rejection) after allografting, RNA was isolated from corneal tissues and cervical lymph nodes (LN). The chemokine mRNA levels of theTh1 axis (CXCL9, CXCL10, CXCL11, CCL5), Th2 axis (CCL1, CCL11, CCL17), and Th17 axis (CCL22, CXCL2) were analyzed by Real-Time PCR.
Results: :
Significant gene upregulation was observed only at the cornea, but not at the LN. The allografts in WT hosts showed a 10- to 1000-fold increase of the gene expression of all Th1- and Th17-type chemokines, but no increase of the Th2 type at both 7 and 21 days postoperatively. In contrast, the allografts in GKO hosts showed no upregulation of CXCL9, CXCL10, and CXCL11 gene expression. However, the gene expression levels of CCL5 and the Th17 type were similar to that of the WT hosts. In addition, a 10- to 100-fold CCL1 and CCL17 gene upregulations were observed at day 21.
Conclusions: :
Though IFN-gamma-associated chemokines were suppressed in GKO hosts, CCL5 (RANTES) may mediate Th1-type cell infiltration. Under the IFN-gamma deficiency, the Th2-type immune response, except that of CCL11 (Eotaxin), may also be associated with graft failure. Therefore, it is necessary to develop an advanced strategy for promoting allograft survival to suppress inflammatory-cell infiltrates at the appropriate time as well as Th1 suppression.
Keywords: transplantation • inflammation • immunohistochemistry