IMMUNE-RESPONSES ASSOCIATED WITH SUSCEPTIBILITY OF C57BL 10 MICE TO LEISHMANIA-AMAZONENSIS/

Leishmaniae are protozoans which, depending upon both the host and par asite species, can cause either a healing or nonhealing infection. Whi le C57BL/10 mice are able to heal following infection with Leishmania major, they fail to heal following infection with Leishmania amazonens is. In order to address the role of Th1 and Th2 cell responses in the outcome of these infections in C57BL/10 mice, gamma interferon (IFN-ga mma) and interleukin-4 (IL-4) production was assessed. While cells fro m L. major-infected C57BL/10 mice produced high levels of EFN-gamma, c ells from L. amazonensis-infected animals produced little or no EFN-ga mma. On the other hand, IL-4 was produced only by cells from L. antazo nensis-infected C57BL/10 mice, but this production was restricted to t he first few weeks of infection. Later in infection, when lesions were evident, no IL-4 was detected. Treatment of BALB/c mice with a monocl onal antibody (11B11) directed against IL-4 induced a dramatic reducti on in L. amazonensis lesions. This reduction was associated with a dec rease in IL-4 levels and an increase in IFN-gamma production. However, only a slight reduction in lesion sizes and parasite numbers was obse rved when anti-IL-4-treated C57BL/10 mice were infected with L. amazon ensis. These results suggest that IL-4 may have an important role in m ediating susceptibility to L. amazonensis in BALB/c mice, as previousl y demonstrated for L. major. More importantly, however, the data sugge st that susceptibility to L. amazonensis in C57BL/10 mice is due to th e absence of a Th1 cell response, rather than to the presence of a Th2 cell response.