IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts.
BALB/c mice are highly susceptible to disseminated infection with the intracellular protozoa Leishmania major. Progression of disease requires in vivo expansion of Th2 CD4+ lymphocytes and is reversed by treatment with anti-IL-4 monoclonal antibody. Inasmuch as IL-2 may be necessary for both the production of IL-4 and differentiation of Th2 cells, the possible contribution of IL-2 to progressive infection was examined. 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 footpad 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 demonstrated a similar protective effect when administered twice weekly for 4 wk. Anti-IL-2-mediated cure of cutaneous leishmaniasis was associated with increased IFN-gamma and decreased IL-4 production by regional 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 levels of IL-2 suboptimal for Th2 expansion in vivo do not inhibit Th1 CD4+ and CD8+ T cell activation and IFN-gamma synthesis. Other cytokines or activation pathways that are either IL-2-independent or synergistic with low levels of IL-2 may account for the appearance of curative T cell responses during treatment with anti-IL-2 antibodies.
Heinzel
F P
FP
Veterans Administration Medical Center, Cleveland, OH 44106.
Rerko
R M
RM
Hatam
F
F
Locksley
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007895:Leishmania tropica / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000628:therapy; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma