IL-2 IS NECESSARY FOR THE PROGRESSION OF LEISHMANIASIS IN SUSCEPTIBLEMURINE HOSTS

BALB/c mice are highly susceptible to disseminated infection with the intracellular protozoa Leishmania major. Progression of disease requir es in vivo expansion of Th2 CD4+ lymphocytes and is reversed by treatm ent with anti-IL-4 monoclonal antibody. Inasmuch as IL-2 may be necess ary for both the production of IL-4 and differentiation of Th2 cells, the possible contribution of IL-2 to progressive infection was examine d. Four weekly injections of anti-IL-2 mAb (S4B6) cured more than 80% of BALB/c mice infected with L. major, as determined by diminished foo tpad swelling and decreased numbers of parasites in infected tissues. Multiple doses of S4B6 were necessary for benefit; a single dose given at the time of infection was ineffective. The anti-IL-2R mAb PC61 dem onstrated a similar protective effect when administered twice weekly f or 4 wk. Anti-IL-2-mediated cure of cutaneous leishmaniasis was associ ated with increased IFN-gamma and decreased IL-4 production by regiona l lymph node cells compared to untreated BALB/c mice with progressive illness. Both CD4+ and CD8+ T lymphocytes contributed to the increased expression of IFN-gamma mRNA in cured mice. These data suggest that l evels of IL-2 suboptimal for Th2 expansion in vivo do not inhibit Thl CD4+ and CD8+ T cell activation and IFN-gamma synthesis. Other cytokin es or activation pathways that are either IL-2-independent or synergis tic with low levels of IL-2 may account for the appearance of curative T cell responses during treatment with anti-IL-2 antibodies.