CCR6 regulates the function of alloreactive and regulatory CD4+ T cells during acute graft-versus-host disease.

The chemokine receptor CCR6 is expressed by CD4+ T cell effector/memory and regulatory effector/memory (TREM) subsets. Here we show that CCR6 modulates graft-versus-host-disease (GVHD) responses in both alloreactive CD4+ T effector cells and regulatory T (Treg) cells. Mortality and morbidity due to acute GVHD were drastically reduced and delayed when naïve T cells were derived from CCR6-deficient donor mice. This deficiency also affected the suppressive ability of Treg cells in GVHD. CCR6-/- Treg cells were able to suppress T cell proliferation in vitro, but their in vivo capacity to downregulate target tissue damage induced by naïve wild type (WT) T cells was impaired. The data demonstrate a requirement for CCR6 in CD4+ T cell function in GVHD, in both effector and regulatory cell subsets.