TARGETED ACTIVATION OF CD8 CELLS AND INFECTION OF BETA-2-MICROGLOBULIN-DEFICIENT MICE FAIL TO CONFIRM A PRIMARY PROTECTIVE ROLE FOR CD8 CELLS IN EXPERIMENTAL LEISHMANIASIS

CD8+ T cells play an important role in the immunologic control of intr acellular pathogens, particularly viruses. Leishmania are obligate int racellular parasites of macrophages in the mammalian host, and previou s studies using deletion of CD8+ cells by administration of mAb to inf ected animals have suggested a protective role for these cells. Two co mplementary approaches were used to define more carefully the role of CD8+ cells in leishmaniasis. In BALB/c mice susceptible to Leishmania major (L. major) infection, targeted activation of CD8+ T cells was at tempted by immunization with nonapeptides derived from the conserved m ajor outer surface protein of the organism, gp63, that contained the c onsensus binding motif for MHC class I H-2K(d) molecules. Two of the n onapeptides induced CTL activity in subsequently infected BALB/c mice that could be elicited against P815 cells pulsed either with peptide o r lysates of L. major. Purified CD8+ T cells from immunized mice had e levated levels of IFN-gamma mRNA transcripts as compared to unimmunize d mice. Despite evidence for activation of CD8+ cells, none of the mic e immunized with nine different peptides alone or in combination were protected from progressive disease. In a second series of experiments, beta2-microglobulin deficient mice that lack CD8+ cells were infected with L. major and the course of infection monitored. These mice cured disease as rapidly as beta2-m +/- and +/+ littermates, and cure was a ssociated with comparable levels of IFN-gamma mRNA in the draining lym ph node population. Neither of these approaches was able to confirm a substantive role for CD8+ T cells in the primary protective response t o L. major.