Different mechanisms underlie the phenomenon of peripheral tolerance. Recently, a new subset of CD4+ T cells, called T regulatory-1 (Tr1) cells, was described which show suppressor functions in vitro and in vivo and are characterized by a predominant production of IL-10 and/or TGF-beta. Tr1 cells have so far been generated experimentally in an IL-10-rich environment and hold promise for exploitation in the suppression of alloreactions and inflammatory or allergic dispositions. However, these cells have not been characterized in infectious diseases. Here we show that in the chronic helminth infection onchocerciasis (river blindness), where patients have relatively little sign of dermatitis despite the presence of millions of small worms in the skin, T cells can be obtained which bear characteristics of Tr1 cells, producing no IL-2 or IL-4 but substantial amounts of IL-10, variable amounts of IL-5, and some IFN-gamma. These cells display elevated amounts of CTLA-4 after stimulation and are able to inhibit other T cells in coculture, in contrast to Th1 and Th2 clones. This is the first time that this type of suppressor T cell has been cloned as naturally occurring during an infectious disease.