Type I regulatory T cells in malaria: of mice and men

Type I regulatory T (Tr1) cells are a population of regulatory CD4(+) T cells implicated in the suppression of pathological immune responses across multiple diseases, but a unifying transcriptional signature of Tr1 identity across disease contexts has not been characterized. In this issue of the JCI, Edward, Ng, and colleagues identified a conserved transcriptional signature that distinguished Tr1 (IL-10(+)IFN-γ(+)) from Th1 (IL-10(–)IFN-γ(+)) cells in human and mouse malaria. This signature implicated genes encoding inhibitory receptors — including CTLA-4 and LAG-3 — and transcription factors — including cMAF. The authors identified coinhibitory receptor expression that distinguished Tr1 cells from other CD4(+) T cell subsets. Furthermore, cMAF — and, to a lesser extent, BLIMP-1 — promoted IL-10 production in human CD4(+) T cells. BLIMP-1 also played a role in supporting the expression of inhibitory receptors. These findings describe a few key features that seem to be conserved by Tr1 cells across multiple species, disease contexts, and marker definitions.