Decline in total T cell count is associated with onset of AIDS, independent of CD4(+) lymphocyte count: implications for AIDS pathogenesis.
We previously reported that blind T cell homeostasis, in which the total T cell count is maintained but the CD4(+) and CD8(+) subset composition of the T cells can vary, fails approximately 1.5 to 2.5 years before the onset of AIDS. The present study was premised on the hypothesis that if failure of T cell homeostasis (i.e., a decline in total T cell counts) is important in the pathogenesis of AIDS, it should be a significant predictor of AIDS after controlling for the CD4(+) lymphocyte count. Data from 1556 homosexual men with sufficient sequential T cell subset measurements were evaluated, representing 11,988 person-visits in men with known clinical outcomes over a period of more than 10 years. Using regression models that incorporated CD4(+) lymphocyte count and HIV-related symptoms (fever, thrush), it was determined that a yearly decline of more than 300 T cells/microliter of peripheral blood was an independent predictor of the onset of AIDS for subjects with CD4(+) lymphocyte counts of <500 cells/microliter. The results support an important role for failure of T cell homeostasis in the pathogenesis of AIDS.
Margolick
J B
JB
Johns Hopkins University School of Public Health, Baltimore, Maryland, 21205, USA.
Donnenberg
A D
AD
Chu
C
C
O'Gorman
M R
MR
Giorgi
J V
JV
Muñoz
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015331:Cohort Studies; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D006679:HIV Seropositivity; D015497:HIV-1; D006706:Homeostasis; D006801:Humans; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*