Antibody-dependent complement-mediated cytotoxicity in sera from patients with HIV-1 infection is controlled by CD55 and CD59

• Published in: The Journal of clinical investigation Vol. 96; no. 3; pp. 1520 - 1526
• Main Authors: Schmitz, J, Zimmer, J P, Kluxen, B, Aries, S, Bögel, M, Gigli, I, Schmitz, H
• Format: Journal Article
• Language: English
• Published: United States 01-09-1995
• Subjects: Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - immunology; AIDS/HIV; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Antigens, CD - blood; CD4-Positive T-Lymphocytes - immunology; CD55 Antigens; CD59 Antigens; Cell Line; Complement Inactivator Proteins; Complement System Proteins - immunology; Flow Cytometry; HIV-1; Humans; Membrane Glycoproteins - blood; T-Lymphocytes - immunology
• ISSN: 0021-9738
• DOI: 10.1172/JCI118190

Various immune mechanisms have been reported to contribute to the progressive destruction of Th cells in HIV-1-infected patients. Among these, complement mediated lysis of infected cells has been suggested. An increased sensitivity of lymphocytes from HIV-1-infected patients to lysis by monoclonal antibodies directed to MHC class I antigen and complement has been directly correlated with a decreased expression of the decay accelerating factor (CD55). It also has been reported that the expression of the membrane inhibitor of reactive lysis (CD59) is decreased during HIV-1 infection. We examined the effect of antibodies in the serum of HIV-1-positive individuals and normal human serum (NHS) as source of complement on several HIV-1-infected cell lines differing in their expression of CD55 and CD59. When HIV-1-infected target cells without membrane expression of CD55 and CD59 were used, a highly significant cytotoxic effect was observed in the presence of heat inactivated anti-HIV-1-positive sera and NHS, while heat-inactivated anti-HIV-1-negative sera and NHS were unable to induce cytolysis. Similar results were obtained using purified IgG isolated from HIV-1-positive sera and either NHS or guinea pig serum as source of complement. Lysis of HIV-1-infected cells correlated with expression of viral antigens on the cell surface. HIV-1-infected CD55 and CD59 positive target cells showed specific lysis, when the function of these molecules was abrogated by blocking antibodies to CD55 and CD59. The finding of anti-HIV-1-specific cytotoxic antibodies in sera from HIV-1-infected patients should be considered in the pathogenesis of the HIV-1-infection.