ccr5dependent homing of naturally occurring cd4 regulatory t cells to sites of leishmania major infection favors pathogen persistence pathogen persistence after clinical cure is a hallmark of many chronic infections previously we showed that naturally occurring cd4cd25 regulatory t ntreg cells rapidly accumulate within chronic dermal sites of leishmania major infection where they suppress antipathogen cd4 t cell responses favor parasite persistence and dermal pathology and consequently control concomitant immunity here we postulated that chemokines might direct ntreg cell homing in sites of infection and show that cd4cd25 ntreg cells compared with normal cd4 t cells preferentially express the ccr5 chemokine receptor which enables them to migrate in response to ccr5 ligands in vitro we show that in contrast to their wildtype wt counterparts ccr5 cd4cd25 ntreg cells resulted in an increased magnitude of parasitespecific interferon gammaproducing cd4 t cells within infection sites dramatically reduced parasite numbers and potent resistance to infection a finding consistent with the clinical outcome of infected ccr5 mice interestingly this resistance was related to an inefficient migration of ccr5 ntreg cells to infected dermal sites compared with wt ntreg cells thus this study shows that ccr5 directs the homing of cd4cd25 ntreg cells to l majorinfected dermal sites where they promote the establishment of infection and longterm survival of the parasite in the immune host