Mice lacking NK cells develop an efficient Th1 response and control cutaneous Leishmania major infection

NK cells are believed to play a critical role in the development of immunit y against Leishmania major, We recently found that transplantation of wild- type bone marrow cells into neonatal tg epsilon 26 mice, which are deficien t in T and NK cells, resulted in normal T cell development, but no or poor NK cell development. Using this novel model we analyzed the role of NK cell s in the development of Th1 response and control of cutaneous L, major infe ction. Mice selectively lacking NK cells (NK-T+) developed an efficient Th1 -like response, produced significant amounts of IL-12 and IFN-gamma, and co ntrolled cutaneous L, major infection. Administration of neutralizing IL-12 Abs to NK-T+ mice during L, major infection resulted in exacerbation of th e disease. These results demonstrate that NK cells are not critical for dev elopment of protective immunity against L, major. Furthermore, they indicat e that IL-12 can induce development of Th1 response independent of NK cells in NK-T+ mice following L. major infection.