Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen.
We investigated CD4+ and CD8+ T cell turnover in both healthy and HIV-1-infected adults by measuring the nuclear antigen Ki-67 specific for cell proliferation. The mean growth fraction, corresponding to the expression of Ki-67, was 1.1% for CD4(+) T cells and 1.0% in CD8(+) T cells in healthy adults, and 6.5 and 4.3% in HIV-1-infected individuals, respectively. Analysis of CD45RA+ and CD45RO+ T cell subsets revealed a selective expansion of the CD8+ CD45RO+ subset in HIV-1-positive individuals. On the basis of the growth fraction, we derived the potential doubling time and the daily turnover of CD4+ and CD8+ T cells. In HIV-1-infected individuals, the mean potential doubling time of T cells was five times shorter than that of healthy adults. The mean daily turnover of CD4+ and CD8+ T cells in HIV-1-infected individuals was increased 2- and 6-fold, respectively, with more than 40-fold interindividual variation. In patients with <200 CD4+ counts, CD4+ turnover dropped markedly, whereas CD8+ turnover remained elevated. The large variations in CD4+ T cell turnover might be relevant to individual differences in disease progression.
Sachsenberg
N
N
Laboratory of Virology and AIDS Center, Division of Infectious Diseases, Geneva University Hospital, 1211 Geneva 14, Switzerland.
Perelson
A S
AS
Yerly
S
S
Schockmel
G A
GA
Leduc
D
D
Hirschel
B
B
Perrin
L
L
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006207:Half-Life; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000166:cytology
D019394:Ki-67 Antigen; D017493:Leukocyte Common Antigens