Antibody-dependent complement-mediated cytotoxicity in sera from patients with HIV-1 infection is controlled by CD55 and CD59.
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.
Schmitz
J
J
Department of Virology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Zimmer
J P
JP
Kluxen
B
B
Aries
S
S
Bögel
M
M
Gigli
I
I
Schmitz
H
H
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018958:CD55 Antigens; D018957:CD59 Antigens; D002460:Cell Line; D003169:Complement Inactivator Proteins; D003165:Complement System Proteins / Q000276:immunology*; D005434:Flow Cytometry; D015497:HIV-1; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D008562:Membrane Glycoproteins; D003165:Complement System Proteins