Central Memory CD4 T Cells from Persons with HIV Accumulate DNA Content Defects During Proliferative Response

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Central memory (T_CM) cells are crucial for maintaining CD4 T cell counts in HIV infection.
• The mechanisms causing T_CM cell loss in HIV remain unclear, despite their increased proliferation.

Purpose of the Study:

• To investigate the cell division and cell cycle behavior of T_CM cells in people living with HIV (PLWH).
• To understand the proneness of T_CM cells to death during HIV infection.

Main Methods:

• Purified circulating T_CM cells from untreated PLWH and healthy controls were stimulated in vitro.
• Cell viability, DNA content, proliferation, and cyclin expression were analyzed over 4 days.

Main Results:

• T_CM cells from PLWH showed a higher frequency of DNA content below G0/G1 compared to controls.
• PLWH T_CM cells with sub-G0/G1 DNA content were more likely to be cycling (expressing cyclin A).
• A greater percentage of PLWH T_CM cells expressed cyclin A within the G0/G1 phase, suggesting a pre-G2/M arrest.

Conclusions:

• HIV-infected T_CM cells accumulate DNA defects during proliferation, leading to cell cycle-dependent death.
• These defects provide a potential mechanism for the increased T_CM cell turnover in HIV infection.