Antibody-dependent cellular cytotoxicity in HIV infections

ADCC is an important immune effector mechanism against tumor and virus-infected cells that can be destroyed by the combined action of specific antibodies of IgG isotype against cell surface-associated antigens and effector cells, predominantly of the NK phenotype. ADCC has been shown to function in vivo in several systems. With regard to HIV, it can be readily demonstrated in vitro against the viral envelope proteins with serum and/or effector cells obtained from HIV-infected subjects. Several studies have demonstrated that the titers of the envy-specific ADCC-mediating antibodies decrease in the sera of HIV-infected individuals as the infection progresses toward AIDS. The cells that mediate ADCC also become functionally compromised in these individuals in early stages of the infection, thus depriving the host of the potential benefits of this process. Restoration of this process in the infected individuals by the administration of functionally competent effector cells (in vitro expanded and lymphokine-activated killer cells) and ADCC-mediating antibodies (hyperimmune serum or appropriate monoclonal antibodies), alone or in combination, may help slow the disease progress. Because of the multicomponent nature of the process, ADCC-mediating antibodies may prove a better correlate of protection and prognosis than the virus-specific neutralizing antibodies and cytotoxic T cells in assessing anti-HIV immunization and immunotherapy.