The role of complement and gp120-specific antibodies in virus lysis and CD4+ T cell depletion in HIV-1-infected patients.
The substantial virus lysis was induced by HIV-1-infected patient serum and normal human complement serum in the presence of purified patient IgG. Non-infected CD4+ T cells coated with the whole virus or with a recombinant HIV-1 envelope gp120 and sensitised with patient IgG were also shown to be susceptible to complement-dependent lysis. The serum level of complement regulatory protein in a fluid phase, the C1-esterase inhibitor, was significantly correlated with serum concentration of C1q-circulating immune complexes (P=0.0062), but inversely with CD4+ T cell count (P < 0.0001). Accordingly, the disease progression in HIV-1-infected patients was significantly correlated with the level of complement activation as determined by serum level of C1-esterase inhibitor (P=0.0001), and inversely correlated with CD4+ cell count (P < 0. 0001) and gp120-specific antibody titre (P=0.0086). These results strongly suggest that the complement activation by gp120-specific antibodies play a very important role in virus clearance, but also in depletion of infected as well as gp120-coated non-infected CD4+ bystander T cells during the course of HIV-1 infection.
Gerencer
M
M
Biomedical Research Center, Immuno AG, Orth/D, 2304, Austria.
Burek
V
V
Crowe
B A
BA
Barrett
N P
NP
Dorner
F
F
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016000:Cluster Analysis; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D054303:HIV Reverse Transcriptase / Q000032:analysis; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D011817:Rabbits; D012588:Scintillation Counting; D018709:Statistics, Nonparametric
D000914:Antibodies, Viral; D003174:Complement C1 Inactivator Proteins; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D003165:Complement System Proteins; D054303:HIV Reverse Transcriptase