Phenotypically distinct subsets of CD4⁺ T cells induce or protect from chronic intestinal inflammation in C. B-17 <i>scid</i> mice

TLDR

CD4+ T cells in mice can be divided into CD45RBhigh and CD45RBlow subsets, which have been shown to be functionally distinct. The authors investigated these subsets by injecting purified CD45RBhigh or CD45RBlow CD4+ T cells into C.B‑17 scid mice. Transfer of CD45RBhigh cells alone induced lethal wasting disease and colitis with high IFN‑γ, whereas CD45RBlow or unfractionated cells did not, and co‑transfer of CD45RBlow cells protected against disease, revealing regulatory interactions.

Abstract

CD4+ T cells in the mouse can be subdivided into two fractions based on the level of expression of the CD45RB determinant. Previous studies have shown that these subsets are functionally distinct. We have further characterized the properties of these subpopulations in vivo by injecting them into C. B-17 scid mice. The animals restored with the CD45RBhighCD4+ T cell population developed a lethal wasting disease with severe mononuclear cell infiltrates into the colon and elevated levels of IFN-γ mRNA. In contrast, animals restored with the reciprocal CD45RBlow subset or with unfractionated CD4+ T cells did not develop the wasting or colitis. Importantly, the co-transfer of the CD45RBlow population with the CD45RBhigh population prevented the wasting disease and colitis. These data indicate that important regulatory interactions occur between the CD45RBhigh and CD45RBlowCD4+ T cell subsets and that disruption of this mechanism has fatal consequences.