Mycobacterium tuberculosis remains one of the top microbial killers of humans causing -2 million deaths annually. More than 90% of the 2 billion individuals infected never develop active disease, indicating that the immune system is able to generate mechanisms that control infection. Rowevo-, the immune response generallyfaib to achieve ste rile clearance of bacilli. Using adoptive cell traiufer into C57BL/6J-Rag1(tm1Mom) mice (Rag1(-/-)), we show that regulatory T cells prevent eradication of tubercle bacilli by suppressing an otherwise efficient CD4(+) T cell respouse. This protective CD4(+) Tcell response was not correlated with increased numbers of IFN-gamma- or TNF-alpha-expressing cells or general expression levels of IFN-gamma or inducible NO synthase in infected organs compared with wild-type C57BL/6 animals. Furthermore, suppression ofprotection 4 cotransferred regulatory T cells was neither accompanied by a general increase of IL-10 expression nor by higher numbers of IL-10-producingCD4(+) Tcells.