Antibody-dependent cellular cytotoxicity to clinical isolates of HIV-1 and SIVcpz: Comparison of humans and chimpanzees

Objective: To investigate differences in the antibody-dependent cellular cytotoxicity (ADCC) responses between HIV-1-infected humans and chimpanzees. Design: The breadth of the ADCC responses in the two populations were tested against autologous and heterologous HIV-1 and SIVcpz clinical isolates as well as against reference isolates. Methods: ADCC was tested in a Cr-51-release assay using human peripheral blood mononuclear cells as effector cells and infected Jurkat/Tat-cells as target cells. Results: The majority of sera from chronically HIV-l-infected humans and chimpanzees had ADCC responses to HIV-1(LAI). Interestingly, vaccinated chimpanzees with a low virus load during the immediate post-challenge period had low ADCC responses 3 years after challenge. In contrast, when ADCC activity to clinical isolates was evaluated, HIV-1-infected chimpanzees had more frequent heterologous (broader) responses than HIV-1-infected humans. ADCC was also tested in consecutive serum samples from two patients and two chimpanzees against autologous isolates, but was only detected to a low degree in one of the animals, although heterologous ADCC was demonstrated in all cases. The naturally infected (SIVcpz) chimpanzee did not have detectable heterologous or autologous ADCC responses. Conclusions: HIV-1-infected chimpanzees had broader ADCC reactivity to heterologous HIV-1 clinical isolates than the HIV-l-infected humans. These findings are consistent with subtle differences in host-virus relationships of these two species.