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 naive 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 naive 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.