gp120-directed antibody-dependent cellular cytotoxicity as a major determinant of the rate of decline in CD4 percentage in HIV-1 disease.
OBJECTIVE
To determine the relationship between the rate of CD4 percentage decline and two factors postulated to be associated with CD4 cell destruction: circulating HIV-1 viral load and gp120-directed antibody-dependent cellular cytotoxicity (ADCC).


METHODS
Four women and 16 men had serial determinations of CD4 percentage gp120-directed ADCC activity [using the cell-mediated cytotoxicity (CMC) assay] natural killer (NK) cell number, spontaneous NK lytic function, and plasma HIV-1 RNA.


METHODS
The rate of decline in CD4 percentage was modeled as a function of gp120-directed ADCC activity and circulating HIV-1 RNA using Pearson correlation and multiple regression analyses.


RESULTS
All individuals had at least four CMC assays performed and two HIV-1 RNA polymerase chain reaction measurements over a median follow-up of 27 months. Although the rate of CD4 percentage decline was associated with either CMC activity (r = -0.53, P = 0.02) or circulating HIV-1 RNA (r = -0.42, P = 0.07), it was strongly correlated with an interaction between CMC and HIV-1 RNA (r = -0.76, P < 0.0001). Mean CMC activity was associated with both mean percentage of circulating NK cells and mean spontaneous NK cell lysis.


CONCLUSIONS
The ability of cells from HIV-infected individuals to mediate gp120-directed ADCC, together with a sufficient circulating viral load, define conditions under which rapid CD4 cell destruction may occur. This relationship between viral load and an HIV-1-specific immune response lends important insights into the central causes of immunodeficiency in AIDS and suggests additional avenues for therapeutic intervention.
Skowron
G
G
Department of Medicine, Roger Williams Hospital, Providence, Rhode Island 02908, USA.
Cole
B F
BF
Zheng
D
D
Accetta
G
G
Yen-Lieberman
B
B
D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008297:Male; D019562:Viral Load
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120