Adoptive transfer of naive T cells into T-cell deficient host mice has been used as a colitis (gut inflammation) model that led to discovery of FOXP3+ T regulatory cells which when co-transferred with naive T cells prevented gut immunopathology.
A new study in Journal of Experimental Medicine, however, provided evidence to show that there is a limit how much FOXP3+ T regs could do. This study found that adoptive transfer of naive T cells into Rip2−/−Rag1−/− mice (RIP2 is an essential signaling adapter molecule downstream of both NOD1 and NOD2) led to protozoa, Tritrichomonas muris-enabled dominant colitis that could not be prevented by FOXP3+ T regs.
Initially, the authors observed in non-littermates that naive T cell transfer led to severe gut inflammation in Rip2−/−Rag1−/− host as compared to just Rag1−/− mice [though it is strange that in their mouse facility Rag1−/− host did not show weight loss after T cell transfer].
Interestingly, colitis in Rip2−/−Rag1−/− hosts could not be prevented by co-transfer of FOXP3+ T regs.
Co-housing and littermate control control experiments confirmed that a non-genetic factor was responsible for colitis development in Rip2−/−Rag1−/− hosts and that factor could be transferred between mice when co-housed together.
Fecal matter analysis showed that Rip2−/−Rag1−/− hosts were selectively enriched with protozoa Tritrichomonas muris, and that its transfer to other mouse accelerated T cell-mediated colitis.
In summary, this study shows that Rip2−/−Rag1−/− double deficient hosts harbor protozoa Tritrichomonas muris that by itself or through modulation of gut microbiota establishes a dominant colitogenic gut ecosystem that is even transferable to genetically non-related mice.