HIV-INFECTION SUPPRESSES TYPE-1 LYMPHOKINE AND IL-12 RESPONSES TO TOXOPLASMA-GONDII BUT FAILS TO INHIBIT THE SYNTHESIS OF OTHER PARASITE-INDUCED MONOKINES

Individuals infected with Toxoplasma gondii normally develop resistanc e to the parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this resistance is lost leading to reactivation of infe ction and development of encephalitis. To characterize the cytokine re sponse of T. gondii-iniected individuals, PBMC were cultured in vitro in the presence or absence of crude tachyzoite Ags (STAg). When stimul ated with STAg, PBMC from T.gondii-infected donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and IFN-gamma) as wel l as the monokine IL-12, in the absence of detectable Type 2 lymphokin es (IL-4 and IL-5). In contrast, cells of individuals from both groups produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag preparation. By using highly purified elutriated cells, we de monstrated that monocytes are a major source of these monokines. The a bove findings were further expanded by analyzing the cytokine response s induced by STAg in PBMC from patients co-infected with T.gondii and HIV. Our results demonstrate that parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before AIDS development, as is IL -12 synthesis by PBMC from HIV-infected individuals stimulated with ST Ag. In contrast, the release of IL-6 and TNF-alpha triggered by STAg i s either not affected or augmented during HIV infection.