Vaccination and treatment trials against murine leishmaniasis with semi-purified Leishmania antigens.

Antigens with molecular weight ranges of 94-67 kDa (LiF2), 30-20 kDa (LiF5), or below 20 kDa (LiF6), isolated from lysates of Leishmania infantum promastigotes by electroelution from polyacrylamide gels were injected into mice which were genetically either partially resistant (C57BL/6) or susceptible (BALB/c) to Leishmania infection. One month after the completion of the intravenous (C57BL/6) or subcutaneous (BALB/c) schedules, the mice were challenged with 1 x 10(3) L. major promastigotes. All mice immunized with LiF2, LiF5 and LiF6 were completely resistant. Furthermore, the C57BL/6 mice immunized with LiF2 resisted a second challenge with 1 x 10(4) L. major amastigotes. 5 months later, LiF2 antigen was used for immunotherapy of L. major leishmaniasis; parasites disappeared from the treated skin lesions, although ensuing systemic infection could not be averted.

Fc-gamma receptor III shedding by polymorphonuclear cells in primary Sjögren's syndrome.

A sandwich enzyme-linked immunosorbent assay was developed to assess Fc-gamma receptor III (Fc gamma RIII), based on a combination of two non-competing monoclonal antibodies. This receptor was detectable in the serum of eight out of 23 patients with primary Sjögren's syndrome and two out of 23 normal controls. The proportion of Fc gamma RIII-carrying polymorphonuclear (PMN) cells was lower (P < 0.05) in the patients with cell-free Fc gamma RIII (90.4 +/- 7.5%) than in the remainder (84.8 +/- 8.3%). The PMN cell functions were evaluated and the diminished adherence (71.7, geometric mean) and chemotaxis (1.23) paralleled the Fc gamma RIII release. The relative inefficiency of PMN cells in SS might be due to phagocytosis of immune complexes.

Study of IL-2 receptor expression after chemoimmunotherapy in patients treated for metastatic malignant melanoma.

Using flow cytometry, cellular IL-2 receptors were studied before and following chemoimmunotherapy combination in 20 patients with metastatic malignant melanoma (MMM). Patients received cisplatin (100 mg/m2) at days 1 and 28, recombinant IL-2 by continuous infusion from days 3 to 6, 17 to 21, 31 to 34, and 45 to 49. Interferon-alpha (IFN-alpha) was given subcutaneously three times weekly. In terms of clinical response, we observed 55% objective response (complete: 15%). When pretreatment blood samples were compared with those of healthy donors, we did not observe any change in low (alpha chain) and high affinity receptor (alpha + beta) expression. In contrast, intermediate affinity p75 (beta chain) expression was decreased significantly (P < or = 0.0001) in MMM patients. During treatment, we found a dramatic increase of beta chain as well as high affinity (alpha + beta) expression in responding patients, as soon as IL-2 therapy began. Furthermore, the increase of beta chain expression was limited to natural killer (NK) cells (CD56+). In non-responding patients, on the other hand, increase of both receptors was seen only at day 31. These data suggest the involvement of beta chain expression in the mechanism of cell activation after chemoimmunotherapy. Moreover, this early beta chain expression is correlated with the clinical response to chemoimmunotherapy.

Follow up of soluble IL-2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy.

Immunological parameters following chemoimmunotherapy combination were studied in 31 patients with metastatic malignant melanoma. They received Cisplatin (100 mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN-alpha; Roche) was given subcutaneously three times weekly. No significant change in CD4/CD8 ratio at onset or during treatment was observed between responder (n = 19) and non-responder (n = 12) patients. Regarding the IL-2 receptor (IL-2R) study, the percentage of cells expressing Tac (p55) receptor did not change either for healthy volunteers (n = 20) and patients before any therapy, or between responder and non-responder patients. Concerning serum soluble IL-2R shedding before therapy, we observed a significant increase (P = 0.001) in patients (79 +/- 40 pM) compared with healthy donors (30 +/- 15 pM), but no significant variation was seen between responder and non-responder patients. In contrast, during the treatment, the soluble IL-2R level increased in both groups but, interestingly, a significant difference was found between responder and non-responder patients from day 7 (P < 0.05) to day 21 (P < or = 0.01), suggesting that the cells from non-responder may be slower in becoming stimulated. This finding is the most striking point of our study and suggests that sIL-2R might be an early predictive factor of the clinical response as obtained by logistic regression (P = 0.0063). Therefore patients with a serum soluble IL-2R level greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical response.