Micromanaging alloimmunity
Mandy L. Ford
Mandy L. Ford
Published June 20, 2016
Citation Information: J Clin Invest. 2016;126(7):2422-2424. https://doi.org/10.1172/JCI88621.
View: Text | PDF
Commentary

Micromanaging alloimmunity

Abstract

Increasing evidence indicates that microbes have a large influence on immune function. Previous studies have linked pathogenic microorganisms with decreased allograft tolerance and subsequent rejection. In this issue of the JCI, Lei and colleagues demonstrate that commensal organisms also influence the host response to allograft transplantation. Using murine skin and cardiac transplant models, the authors demonstrate that allograft rejection is accelerated in mice with a normal microbiome compared with germ-free animals and antibiotic-treated mice. The increased graft rejection observed in conventional animals was due to enhanced T cell priming and was mediated through type I IFN. Together, these results suggest that altering a patient’s microbial community prior to transplant could improve allograft acceptance.

Authors

Mandy L. Ford

×

Figure 1

Commensal microbiota affect alloreactive T cell responses by enhancing APC activation in a type I IFN–dependent manner.

Options: View larger image (or click on image) Download as PowerPoint
Commensal microbiota affect alloreactive T cell responses by enhancing A...
(A) Exposure of the intestinal and/or skin epithelium to commensal microbes results in systemic alteration of APCs, an effect that can be detected in the LNs. Gene-expression profiles of these APCs reveal upregulation of the type I IFN pathway, and functional studies show that these APCs have increased capacity to prime donor-reactive T cells, which in turn mediate accelerated rejection of an allograft. (B) Allograft survival was improved in GF mice. Alteration of the microbiome with antibiotics also improved allograft survival.