Category: Organ transplantation
The inflammatory cytokine IL-6 contributes to immune activation that causes acute and chronic rejection of organ transplants. However, very little is known about the signaling mechanisms by which IL-6 functions in this setting. IL-6 can transduce signals that lead to distinct biological outcomes through mechanisms that are either dependent or independent of IL-6 receptor (IL-6R) expression on the surface of target cells. Using mice that lack IL-6R expression only in T cells (IL-6R-TKO) and a murine aortic interposition model of vascular rejection, we examined the role of IL-6R in T cells on allogeneic immune responses. IL-6R-TKO mice were generated by crossing IL-6Rflox/flox mice with CD4-Cre partners. IL-6R expression was absent in T cells from IL-6R-TKO mice but remained abundant on other leukocyte lineages. There was no difference in the accumulation of CD4 and CD8 T cells in allograft arteries from IL-6R-TKO graft recipients as compared to IL-6Rflox/flox control counterparts. IL-6R expression on T cells also did not affect the accumulation of macrophages in allograft arteries. When donor-specific antibodies (DSA) were examined, their de novo generation was apparent 2 – 3 weeks after transplantation, remained high thereafter, and was markedly and significantly reduced in IL-6R-TKO graft recipients as compared to controls. Overall, our findings indicate that IL-6R expression in T cells is dispensable for the development of peripheral effector T cell responses towards vascular allografts but is needed for the development of DSA.
Ashani Montgomery– Graduate trainee, Simon Fraser University
Kevin Rey– Graduate trainee, Simon Fraser University
Winnie Enns– Technician, Simon Fraser University
Naomi Giesbrecht– Honor's student, Simon Fraser University
Catherine Cheneval– Technician, Simon Fraser University
Jonathan Choy– Associate Professor, Simon Fraser University