J. Exp. Med., Volume 187, Number 8, April 20, 1998 1295-1303

Turnover of CD4⁺ and CD8⁺ T Lymphocytes in HIV-1 Infection as Measured by Ki-67 Antigen

By Nicolas Sachsenberg,^* Alan S. Perelson, Sabine Yerly,^* Gérard A. Schockmel,^* Dominique Leduc,^§ Bernard Hirschel,^* and Luc Perrin^*

From the ^* Laboratory of Virology and AIDS Center, Division of Infectious Diseases, Geneva University Hospital, 1211 Geneva 14, Switzerland; the  Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545; and ^§ Ambilly Hospital, Annemasse 74100, France

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.

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