Contribution of the Microbiome to Maintenance of the CD4:CD8 Ratio in Inbred and Congenic Mouse Strains

Abstract

Abstract The gut microbiome is known to play an integral role in the regulation of the immune system. Previous studies indicate that species diversity and overall abundance of commensal bacteria in the gut influences immune system function by altering total T cell counts and the ratio of CD4+ to CD8+ T cells in peripheral lymphoid organs and blood. In normal individuals, the CD4:CD8 ratio is greater than one. However, the congenic B10.A mouse strain in our conventional facility consistently demonstrates an inverted CD4:CD8 ratio in a sex- and age-dependent manner, in contrast to both the parental C57Bl/10 strain and B10.A kept under SPF conditions. To determine whether this phenomenon is due to the composition and diversity of the gut microbiome affecting the homeostasis of the CD4:CD8 ratio, we altered the microbiome by supplementing the diet with the prebiotic inulin and looked for changes in the number of Peyer’s patches and changes in the CD4:CD8 ratio in gut lymphoid organs and blood in both B10.A and C57Bl/10 strains. In addition, we followed the changes in the microbiome upon treatment. We find that the mice in our facility have lower microbiome diversity and very different composition from mice kept at SPF conditions. The inulin treatment significantly increased the CD4:CD8 ratio in the blood of the C57Bl/10 mice, but not the B10.A mice. In addition, males of both strains had a significant increase in Peyer’s patch number, while the females had a significant increase in the CD4:CD8 ratio in the Peyer’s patches.