Table II.
Cure of Leishmaniasis after GK1.5-based Immunotherapy Is Associated with Unipolar Th1-type Cytokine Responses
| Group | Antigen-induced cytokine levels | |||
|---|---|---|---|---|
| IFN-γ | IL-4* | |||
| ng/ml ± SEM | ||||
| Experiment 1 | ||||
| Control (n = 5) | 1.42 ± 0.19 | 1.24 ± 0.35 | ||
| Immunotherapy (n = 5) | 0.88 ± 0.39 | 0.06 ± 0.02 | ||
| Experiment 2 | ||||
| Uninfected | 0.11 | ≤0.05 | ||
| Control (n = 5) | 1.36 ± 0.07‡ | 1.28 ± 0.17 | ||
| Immunotherapy (n = 3) | 1.01 ± 0.12‡ | 0.05 | ||
| Nonhealing (n = 2)§ | 2.08 | 1.53 | ||
BALB/c mice were treated with GK1.5 and 11B11 mAb, followed by intralesional rIL-12 as described in the text. Lymph node cells were harvested after disease recovery at wk 4 of reinfection (Experiment 1) or at wk 7 after immunotherapy (Experiment 2) and were cultured for 48 h in the presence of 10 μg/ml of soluble leishmania antigen. Cytokine concentrations were measured by specific ELISA. Control lymph node cells were from BALB/c mice infected for 4 wk with L. major.
IL-4 was measured in antigen-stimulated cultures to which anti–IL-4 receptor mAb had been added (10 μg/ml). IL-4 levels in all cultures were reduced by >96% in the presence of anti–MHC II mAb.
Antigen-stimulated IFN-γ production was reduced 60.8 ± 5.4% for control mice and 46.3 ± 7.5% for immunotherapy mice after neutralization of MHC II by anti–I-Ed/I-Ad mAb added at 10 μg/ml to antigen-stimulated cultures.
Two mice failed therapy, as indicated by chronic footpad swelling and cutaneous ulceration.