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ryosuke motohashi, Takaaki Hattori, yosihiko usui, hayate nakagawa, hisaya akiba, Hiroshi Goto; Suppression Of Corneal Graft Rejection By Blocking Cd27/cd70. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2371.
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© ARVO (1962-2015); The Authors (2016-present)
CD70 is the costimulatory molecule expressing on antigen presenting cells which bind with CD27 expressing on T and B cell to derive immunological response. It has been known that blockade of CD27/CD70 suppress alloreactivity of CD8 T cell during organ transplantation, and do so, promoting allograft survival. In contrast, the role of CD27/CD70 on alloreactive CD4 T cell is still unclear. Therefore, we investigated the role of CD27/CD70 on corneal transplantation which is known as a model of CD4 T cell dependent allograft rejection.
C57BL/6 mice corneas were transplanted to Balb/c mice. To evaluate the expression of CD27 and CD70 after graft rejection, we performed immunohistochemical staining of corneas harvested from mice which rejected donor corneas with anti-CD27 and anti-CD70 antibody. Anti-CD70 antibody (FR70) which inhibit CD27/CD70 interaction were administrated to the recipient mice intraperitoneally (300ug/ml, three times per week) from day 0 to 3 weeks post-transplantation (n=7). Rat IgG was administrated as the control group (n=8). T cells were harvested from cervical lymph nodes at 3 weeks post-transplantation to measure the alloreactivity by MLR (mixed lymphoid reaction). We also examined the expression levels of IFN-γ in corneas from each group by real-time PCR. Rejection reaction was observed by slit-lamp microscopy until 8 weeks post-transplantation.
Immunohistochemical staining of corneas from rejected mice revealed that positive expression of CD27 on CD4 positive cells and CD70 was expressed on CD11c positive cells in recipient corneas. MLR results showed that FR70 treatment suppress alloreactivity of recipient T cells compared to control IgG treated group. Expression of IFN-γ was also reduced in FR70 treated group corneas. Finally, FR70 administration significantly suppressed corneal graft rejection at 8 week post-transplantation.
Our results suggest that CD27/CD70 promote CD4 T cell dependent alloreactivity in addition to CD8 T cell alloreactivity. Thus, application of anti-CD70 antibody treatment will be potential therapy for the rejection of corneal transplantation.
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