Search

An anti-idiotype serum was raised in a chimpanzee (A) by immunization with autologous lymphocytes primed in vitro against an unrelated chimp (B). This autoantiserum in the presence of complement was cytotoxic for 5 to 7% of the resting lymphocytes from chimp A and for 30 to 45% of the mixed lymphocyte culture (MLC) primed cells (A X Bx), but was not reactive against the lymphocytes of the priming chimp (B). Anti-idiotype antibody and complement treatment of autologous resting or primed cells blocked the ability of these cells to respond in MLC or primed lymphocyte test (PLT) to the stimulator cells from chimp B, but not to cells from a third chimp. When cells from the immunized animal (A) were incubated with the autologous antiserum in vitro, they were stimulated, thus producing cells which had the same activity in PLT as did cells primed against stimulator cells of chimp B. Thus, an autoanti-idiotype serum has been raised in a primate system which identifies the recognition structure on autologous T cells directed against antigeneic determinants on the stimulator cells of a histoincompatible donor.

The present study evaluated the activity of ketoconazole in neutropenic dogs with systemic candidiasis. Five dog pairs were made neutropenic by intravenous cyclophosphamide (50 mg/kg) and challenged with either 10(6) or 10(7) colony-forming units (CFU) of Candida albicans. Half of the dogs received ketoconazole (10 mg/kg) daily beginning 24 h after challenge. All were killed at 96 h and liver, spleen, and kidney were cultured. Of four dogs given 10(6) CFU, two untreated dogs had 9 X 10(3) to 1 X 10(5) CFU/g wet tissue, compared to 0 CFU in ketoconazole-treated dogs. With inoculum increased to 10(7) CFU, three untreated dogs had 2 X 10(4) to 3 X 10(5) CFU/g wet tissue, while three ketoconazole dogs had 0-5 X 10(3) CFU/g wet tissue. The effect of ketoconazole on autologous marrow reconstitution in dogs with systemic candidiasis was examined by infusing autologous cryopreserved marrow into four dogs one day after lethal whole body irradiation (800 rad). Once neutropenic, they were challenged with 10(7) CFU of C. albicans. Two dogs received no ketoconazole and died of disseminated candidiasis, without marrow reconstitution. Two dogs received ketoconazole for 25 days. Prompt marrow recovery occurred and they remained healthy. There was no evidence of infection at death. These studies quantitatively demonstrate the in vivo effectiveness of ketoconazole in reducing tissue infection with C. albicans in neutropenic dogs. They provide in vivo evidence that ketoconazole can prevent or cure systemic candidiasis in the bone marrow transplant setting without significant inhibition of marrow recovery.

As a model to study the possible early side effects of cultured T-cells (CTC) as a potential for adoptive cellular immunotherapy of human tumors, chimpanzees received iv infusions of 10(9) autologous, mixed lymphocyte culture-primed CTC. Complete blood counts, urinalyses, chest X-rays, blood chemistries, and serum immunoelectrophoresis were normal, and serologic studies were negative throughout the 3 weeks of observation. Serial transaminase levels were followed in 2 chimps, and mild increases in serum glutamic-oxaloacetic transaminase were seen in both and serum glutamic-pyruvic transaminase in 1 at 24 hours following each CTC infusion, but the levels returned to normal within 7 days. A liver biopsy specimen was normal. Fluorescence-activated cell sorter analysis of cells incubated with day 28 serum revealed weak labeling of only phytohemagglutinin (PHA)-stimulated lymphoblasts and of CTC, suggesting that a weak anti-PHA antibody was generated. These studies indicate that infusions of autologous, in vitro-primed CTC are accompanied by little clinical toxicity in the chimp model but that they may be weakly immunogenic.