The basic defect in lepromatous leprosy is the selective unresponsiveness of T cells to the antigens of Mycobacterium leprae (1). This defect may be partial or complete (2) and does not appear to change with prolonged chemotherapy (3). A lack of T cell-derived lymphokines such as IFN-y and IL-2 could account for the inability of macrophages and other cells to eliminate M. leprae .Attempts to circumvent T cell unresponsiveness have already been initiated in both in vitro systems (2, 4-6) and in the confines of the cutaneous lesions. Initial observations have been reported on the efficacy of crossreacting antigens such as purified protein derivative of tuberculin (PPD)' and the lymphokine rIFN-. y (7-10) . In the case of PPD, intradermal administration has led to a long-lived emigratory mononuclear leukocyte response, the local destruction of parasitized macrophages, and a striking reduction in the number of M. leprae within 21 d. These responses and the accompanying modification of cellular subsets are evidence of a vigorous cell-mediated immune reaction in the environment ofa lepromatous lesion . Similar observations have been made after IFN-y administration (manuscript in preparation).We have now extended these observations to the use of human rIL-2. This lymphokine serves as an autocrine T cell growth factor, and induces the formation of lymphokines with other functions (11,12). We report results on the use of small doses of IL-2, in the skin of lepromatous patients, and the reconstitution of cutaneous cellular immunity. Volume 169 March 1989 893-907 Materials and Methods Patient Population . 35 patients, 18-60 yr old, 23 with lepromatous leprosy (LL) and 12 with borderline lepromatous leprosy (BL) (13), were selected for the intradermal administra-

Treatment of diffuse cutaneous leishmaniasis (DCL) caused by Leishmania aethiopica remains unsatisfactory as the parasite is relatively insensitive to antimonial compounds. Reports of the clinical effectiveness of aminosidine sulphate, especially in combination with sodium stibogluconate, in visceral leishmaniasis and the finding that this antibiotic is potent against L. aethiopica in vitro, prompted us to evaluate its usefulness in DCL. Two patients with long-standing, active DCL were treated for 60 d with aminosidine sulphate, 14 mg/kg/d parenterally. The skin lesions resolved completely in both patients although they relapsed subsequently. Synergism between aminosidine and stibogluconate was demonstrated in vitro against parasites isolated from the patients. This led us to administer combined therapy, aminosidine sulphate 14 mg/kg/d and sodium stibogluconate 10 mg/kg/d, to the 2 patients in relapse and to another, third patient. Treatment was continued for 2 months beyond parasitological cure. Side effects were minimal. Following treatment, a return of specific cell-mediated immunity occurred, as expressed by a moderate infiltration of lymphocytes into the lesions and by lymphocyte proliferation in vitro in the presence of live Leishmania antigen, with synthesis of interleukin-2 and interferon gamma with one patient and interleukin 4 with the other. During follow-up periods of 2 to 21 months after treatment, no sign of relapse was seen.

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Three patients with disseminated cutaneous leishmaniasis received three intranodular injections of 10 micrograms of recombinant interleukin 2 (rIL-2) at 48-h intervals. After 7 and 14 days, 4-mm punch biopsies were taken of control and injected nodules and processed for histology, electron microscopy, immunocytochemistry, and parasite culture. Control sites exhibited loose infiltrates of parasitized macrophages and T cells predominantly of the CD8+ phenotype. Amastigotes were present in large numbers and were found distributed within tightly apposed endosomes and larger vacuoles. After the administration of rIL-2, there was a prominent influx of T cells, predominantly of the CD4+ phenotype, and an increased number of plasma cells. At 7 days, leishmanial amastigotes were present in either the same or somewhat reduced numbers but predominantly within large, lucent vacuoles. By 14 days the number of amastigotes was strikingly lower. Lymphokine-treated skin sites became sterile in two patients, as evaluated by parasite culture after rIL-2 injection. The results suggest that the local administration of rIL-2 induces a beneficial enhancement of the cellular immunity with a consequent disposal of parasites in the cutaneous site.