An avirulent lipophosphoglycan-deficient Leishmania major clone induces CD4+ T cells which protect susceptible BALB/c mice against infection with virulent L. major

Abstract

An avirulent clone of Leishmania major was used to immunize susceptible BALB/c mice against challenge with virulent L. major. By using the immunized animals as a source of cells, CD4+ parasite-specific T-cell lines could be generated in vitro which, when adoptively transferred to naive BALB/c recipients, conferred marked protection against challenge with virulent L. major. Compared with CD4+ parasite-specific T-cell lines generated from nonimmunized BALB/c mice infected with L. major, the protective T-cell lines generated from immunized mice produced substantially less interleukin-4 and substantially more tumor necrosis factor and interleukin-2. Interestingly, the protective CD4+ T cells did not mediate L. major-specific delayed-type hypersensitivity in vivo and proliferated in vitro only in response to living L. major and not to frozen-and-thawed antigen preparations of the parasite. Finally, the avirulent clone of L. major was found to express the major surface glycolipid of L. major, lipophosphoglycan, at a level that was sixfold less than expression of this molecule by virulent L. major. In addition, lipophosphoglycan of the avirulent parasite failed to mature into the larger, or metacyclic, form of the molecule.