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.