Background: The dynamic basis for CD4 T-cell depletion in AIDS remains controversial.

Methods: To address this major issue, we explored T-cell dynamic using a new sensitive fluorescent assay to determine direct measurement of circulating T-cell kinetics in peripheral blood of pathogenic and apathogenic SIV-infected macaques. Results: In pathogenic SIV-infected macaques, we found after transfer of CFSE-labeled cells that 1) T-cell dynamic of CD4⁺ and CD8⁺ T-cells is profoundly different indicating no proliferation of CD4⁺ T cells compared with CD8⁺ T-cells; and 2) the lifespan of circulating CD4⁺ and CD8⁺ T-cells is shorter than in the uninfected macaque correlating with progression towards AIDS.

We also found in peripheral blood as well as in the axilary lymph nodes that the absolute number of cycling CD4⁺ T-cells is not increased in SIVmac251-infected macaques as compared with uninfected or apathogenic SIV∆nef-infected macaques. The number of Ki67⁺CD4⁺ T-cells even declined drastically in peripheral blood of severe progressor SIV-infected macaques (ranging from –40% to –70%). In opposite, the numbers of cycling CD8⁺ T-cells increased by 2–4 fold in the blood of SIVmac251-infected macaques as well as in the lymph nodes (by 2–8 fold) and is correlated with disease progression towards AIDS.

Conclusion: Altogether, these results indicated that CD4 T-cell lymphopenia is essentially due to a shortened survival, but not to an increase in the turnover of these cells.