CD4+Ki67+ lymphocytes in HIV-infected patients are effector T cells accumulated in the G1 phase of the cell cycle

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Abstract
Entry into the cell cycle represents a fundamental step before generating an effector immune response. The relationship between the cell cycle and antigen-driven T cell response remains, however, poorly understood in virus infection, including HIV. We have identified a critical fraction of CD4+CD45RO+ memory T lymphocytes that express the Ki67 antigen in chronically HIV-infected patients. A high accumulation of Ki67 protein is detected in CD4+CD45RO+Ki67+ cells that are in the G1 phase of the cell cycle (92 ± 5 %) but not in S and G2 + M phases, in contrast to normal individuals. Of these cells, 20 – 60 % are spontaneously producing IL-2 and IFN-γ, unlike CD4+CD45RO+ that do not express Ki67. In addition, HIV-p24 antigen is detectable only in a small fraction CD4+Ki67+ cells. In conclusion, CD4+Ki67+ lymphocytes are circulating effector cells accumulated in the G1 phase of the cell cycle and may be involved in the immune surveillance during HIV infection.