Apoptosis of CD4+ and CD19+ cells during human immunodeficiency virus type 1 infection--correlation with clinical progression, viral load, and loss of humoral immunity.
Enhanced rates of programmed cell death (apoptosis) have been detected in T cells and B cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals. To evaluate the possible relevance of this event to HIV pathogenesis and disease progression, apoptosis in CD4+ T lymphocytes and CD19+ B lymphocytes, viral load, and neutralizing antibody titers were assayed in HIV-1-infected slow progressors and progressors. A correlation was found between progressive disease and apoptosis of CD4+ T cells. The extent of apoptosis in CD4+ cells was similar in slow progressors and seronegative control subjects. By contrast, we found elevated levels of B-cell apoptosis in all HIV-1-infected individuals compared with seronegative control subjects, with a tendency toward increased levels of apoptosis with progressive disease. Apoptosis in CD4+ T cells and CD19+ B cells correlated with viral RNA levels in plasma. Furthermore, higher rates of B-cell apoptosis were observed in individuals with poor neutralizing activity against a panel of six clinical HIV-1 isolates. From these results we conclude that the extent of apoptosis in cultured CD4+ cells and CD19+ cells appears to parallel the decline in CD4 cell counts in infected individuals. The finding of a relation between apoptosis in B cells and poor neutralizing capacity suggests that apoptosis may be related to loss of immune function. A role for apoptosis in the pathogenesis of AIDS is also supported by the strong correlation between viral load and rates of apoptosis in CD4+ T cells.
Samuelsson
A
A
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Broström
C
C
van Dijk
N
N
Sönnerborg
A
A
Chiodi
F
F
D000917:Antibody Formation; D018941:Antigens, CD19 / Q000276:immunology*; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D018941:Antigens, CD19; D015483:HIV Antibodies; D012367:RNA, Viral