AN AVIRULENT LIPOPHOSPHOGLYCAN-DEFICIENT LEISHMANIA-MAJOR CLONE INDUCES CD4(-CELLS WHICH PROTECT SUSCEPTIBLE BALB() T)C MICE AGAINST INFECTION WITH VIRULENT L-MAJOR/

An avirulent clone of Leishmania major was used to immunize susceptibl e BALB/c mice against challenge with virulent L. major. By using the i mmunized 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 challe nge with virulent L. major. Compared with CD4(+) parasite-specific T-c ell lines generated from nonimmunized BALB/c mice infected with L. maj or, the protective T-cell lines generated from immunized mice produced substantially less interleukin-4 and substantially more tumor necrosi s factor and interleukin-2. Interestingly, the protective CD4(+) T cel ls 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. Finall y, the avirulent clone of L. major was found to express the major surf ace glycolipid of L. major, lipophosphoglycan, at a level that was six fold less than expression of this molecule by virulent L. major. In ad dition, lipophosphoglycan of the avirulent parasite failed to mature i nto the larger, or metacyclic, form of the molecule.