The microbiota accelerates skin graft rejection through enhanced T cell priming (TRAN1P.953)

Abstract

Abstract The microbiota is known to influence local and systemic immune responses. To test whether the microbiota can modulate the strength of an alloresponse, we used a minor mismatched (H-Y) skin transplant mouse model in both germ-free (GF) and antibiotic-pre-treated (Abx) mice. Abx mice showed a marked reduction in bacterial diversity of their intestinal and skin flora. Skin allograft survival more than doubled in either GF or Abx mice compared to controls and colonization with a complex microbial community from conventional mice was sufficient to restore faster rejection kinetics in GF mice. Mechanistically, CFSE-labeled CD4+ anti-H-Y Marilyn T cells displayed a decrease in proliferation following in vivo adoptive transfer into Abx hosts as well as after in vitro culture with antigen presenting cells from Abx mice. Together, these data indicate decreased priming of allogeneic T cells when the diversity of resident bacterial communities is diminished. This effect is not due to a reduction in bacterial load but rather a loss of taxon-specific host-microbe interactions. This study illustrates the profound systemic effects of the microbial environment in transplant recipients and points to the microbiota as a potential therapeutic target for enhancing graft acceptance.