ID: 100: Regulation and B-cell help mediated by distinct subsets of IL10-producing T-cells
IL10 is a B-cell growth factor produced by CD4 + helper T-cells, but it also mediates suppression of T-cell responses by regulatory T-cells. We found that IL10-producing regulatory T-cells (Tr1) and IL10-dependent B-helper T-cells are distinct subsets in humans and mice. Tr1 cells that suppressed T cell proliferation and experimental colitis co-expressed CCR5 and PD1, but not CCR6 or IL-7R. They down-regulated IL-10 production in response to pro-inflammatory cytokines, and consequently produced only low levels of IL-10 in the intestine of IBD patients. Tr1 cells failed to up-regulate CD40L and did not promote B-cell responses, but conversely suppressed IgG production. However, Tr1 cells from lupus patients were unable to inhibit B cell responses. In marked contrast, IL10-producing IL-7R + CCR6 + helper T-cells expressed CD40L and induced B-cell antibody production via IL10. Notably, these IL10-dependent B-helper T-cells were distinct from conventional TFH and Th17-cells, were auto-reactive and consequently provided spontaneous B cell help in lupus patients. In summary, we defined a strategy to distinguish IL10 producing T-cell subsets with opposing functions in B-cell responses and in autoimmune diseases.