April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
The Role of Neutrophil Mediated Corneal Allograft Rejection in C57BL/6-IFN-Gamma KO Hosts
Author Affiliations & Notes
  • J. Yamada
    Ophthalmology, Meiji University of Integrative Medicine, Kyoto, Japan
    Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • J. Hamuro
    Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • T. Ohteki
    Immunology, Akita University School of Medicine, Akita, Japan
  • K. Terai
    Ophthalmology, Meiji University of Integrative Medicine, Kyoto, Japan
    Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • S. Kinoshita
    Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Footnotes
    Commercial Relationships  J. Yamada, None; J. Hamuro, None; T. Ohteki, None; K. Terai, None; S. Kinoshita, None.
  • Footnotes
    Support  The Japanese Ministry of Education Grant 19592046
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1975. doi:
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      J. Yamada, J. Hamuro, T. Ohteki, K. Terai, S. Kinoshita; The Role of Neutrophil Mediated Corneal Allograft Rejection in C57BL/6-IFN-Gamma KO Hosts. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1975.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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