Publications

BALB/c mice infected with Leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of CD4+ T cells in the draining lymph nodes. The immune response has been further characterized by a lack of IFN-gamma mRNA, but increased IL-4 mRNA in lymphoid tissues, and striking elevation of serum IgE. Treatment of infected BALB/c mice with rIFN-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate L. major infection. In contrast, neutralization of IL-4 by six weekly injections of mAb 11B11 led to attenuation of disease in 100% of animals, and complete cure in 85%. Resolution of disease required the presence of T cells, and recovered mice remained resistant to reinfection at 12 wk. This immunity was adoptively transferable and was dependent on both CD4+ and CD8+ cells. Although administration of anti-IL-4 was associated with fourfold increase in IFN-gamma mRNA in lymph node cells draining the lesion, the coadministration of neutralizing R4 6A2 anti-IFN-gamma mAb had no effect on resistance to disease. This was in marked contrast to resolution of disease in both resistant C57BL/6- and GK1.5-pretreated BALB/c mice that was abrogated by in vivo treatment with anti-IFN-gamma. These data suggest a novel mechanism of cellular immunity established by interference with the development of Th2 cells during infection.

To clarify further the epidemiology of AIDS-related Kaposi's sarcoma (KS) in San Francisco, we reviewed AIDS cases reported to the San Francisco Department of Public Health through August 31, 1990. Of the 7,119 patients reported, 2,346 (33%) had been diagnosed as having KS: 1,716 (73%) as their presenting clinical manifestation of AIDS and 648 (27%) as a later manifestation. Of these 2,364 KS patients, 2,075 (88%) were homosexual or bisexual men without histories of intravenous drug use, and 273 (12%) were homosexual or bisexual intravenous drug users. From 1981 to August 1989, the proportion of AIDS patients presenting with KS declined from 55 to 19% (p less than 0.001). However, the number of patients being diagnosed with KS has increased along with the overall number of AIDS patients, but this increase was less than the increase in number of patients with other opportunistic infections and malignancies. KS patients were less likely than patients without KS to be reported through an active surveillance system and less likely to be found through retrospective reviews of medical records, death certificates, and obituaries. We conclude that the proportion of AIDS patients with KS is continuing to decline in San Francisco and that this decline is not an artifact of the AIDS surveillance system.

To evaluate survival for AIDS patients diagnosed with Kaposi's sarcoma (KS), we calculated survival for 1,015 patients reported in San Francisco between July 1981 and December 31, 1987, representing 22% of total patients reported. These patients had a definitive initial diagnosis of KS, and developed no other diseases within 3 months of diagnosis. Patients were followed prospectively through December 31, 1988. All patients evaluated in this study were men. Survival was evaluated for subgroups based on age, race and ethnicity, year of diagnosis, and transmission category. The median survival for patients diagnosed with KS alone was 17.0 months, with a 5-year survival rate of 8.7%. Poorer prognosis was found for patients with older age at diagnosis and with later year of diagnosis. Proportional hazards analysis indicated that age (p less than 0.001) and year of diagnosis (p less than 0.05) were significant independent predictors of survival, while race or ethnicity and risk group were not.