Antibody‐dependent cellular cytotoxicity in HIV infections

Abstract

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.

Role of Neutralizing Antibodies in Protective Immunity Against HIV

“…The killing of virus-infected cells by ADCC involves cytotoxic cells (such as NK cells) and may contribute to elimination of the virus. [23][24][25][26] Alsmadi and Tilley 27 studied the ability of human and chimpanzee mAbs directed against cluster II overlapping epitopes of gp41, CD4 binding site, V3 loop and C5 domain of gp120 for their ability to induce ADCC. They demonstrated that mAbs directed against conserved epitopes generally exhibited ADCC activity against a broader range of HIV-1 strains than those directed against variable epitopes.…”

Sustained Impairment of IFN-γ Secretion in Suppressed HIV-Infected Patients Despite Mature NK Cell Recovery: Evidence for a Defective Reconstitution of Innate Immunity

“…A dysfunction of NK cells is present in the course of HIV infection, as indicated by a decrease in NK cell numbers (5)(6)(7)(8)(9) and MHC-nonrestricted (10) and Ab-dependent cell-mediated cytotoxicity (6,(11)(12)(13). In addition to their role in antiviral immunity (14 -16), NK cells produce cytokines and chemokines with antiviral activity (17,18) and IFN-␥, which may directly contribute to HIV control and lack of disease progression.…”

Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease Severity

“…Specifically, NK cells in viremic, chronically HIV-1-infected individuals have decreased natural cytotoxicity (as measured by the killing of the prototypic NK cell target K562 cell line) (38 -42) and decreased Ab-dependent cellular cytotoxicity (ADCC) (41,(43)(44)(45). However, a study by Alter et al has shown that even though viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, the overall NK cell activity is increased (46).…”