Downregulation of Bcl-2, but not of Bax or Bcl-x, is associated with T lymphocyte apoptosis in HIV infection and restored by antiretroviral therapy or by interleukin 2

The role of Bcl-2, Bar, and Bcl-x in the apoptosis of T lymphocytes in HIV- infected individuals was investigated, A strong correlation between Bcl-2 d ownregulation and spontaneous apoptosis has been reported by various groups in short-term cultures of CD8(+) but not of CD4(+) T lymphocytes. We descr ibe a similar correlation in CD4(+) T cells and provide an explanation why Bcl-2 downregulation in these cells has not been detected so far. In apopto tic cells not only Bcl-2, but also the CD4 surface receptors, are downregul ated, preventing the detection of these cells in flow cytometric analysis, In contrast to Bcl-2, no correlation is detectable between Bar or Bcl-x exp ression and apoptosis. T lymphocytes of HIV-infected, but not of control, i ndividuals display ex vivo a heterogeneous Bcl-2 expression pattern with a low and a high Bcl-2-expressing lymphocyte fraction. The proportion of low Bcl-2-expressing T cells correlates with a higher viral load in these indiv iduals, Antiretroviral therapy significantly reduces the proportion of low Bcl-2-expressing lymphocytes, which is associated with a decrease in apopto sis, Bcl-2 downregulation and spontaneous apoptosis of T lymphocytes from H IV-infected individuals can be partially prevented by the exogeneous additi on of IL-2, but not of IL-12, IL-4, or antibodies that prevent the CD95/CD9 5 ligand pathway of apoptosis.