Naive CD4(+) T lymphocytes express high levels of Bcl-2 after highly active antiretroviral therapy for HIV infection

The mechanism causing the increasing number of peripheral T cells after hig hly active antiretroviral therapy (HAART) is still unclear. The bcl-2 oncog ene prevents spontaneous apoptosis (SA) in lymphocytes. Spontaneous apoptos is could be a determinant of HIV immunodeficiency and can be reversed by HA ART including protease inhibitors (PI-HAART). The aims of our study were to measure Bcl-2 protein expression in memory (CD45RO(+)) and naive (CD45RO(- )) CD4(+) and CD8(+) T lymphocytes of HIV+ patients and to correlate it wit h efficacy of PI-HAART. Forty-nine HIV+ patients (cases) and 26 HIV- indivi duals (controls) were evaluated. Patients receiving PI-HAART, and who had u ndetectable HIV plasma viral load (VL-, n = 21), had higher levels of Bcl-2 than did VL+ patients (n = 28), both in CD4(+) cells (p<0.0001) and in CD8 (+) cells (p < 0.001). VL+ patients had lower Bcl-2 levels than did control s in CD8(+) cells (p = 0.02), but not in CD4(+) cells (p>0.05). Interesting ly, VL- patients had higher Bcl-2 expression than did controls both in CD4( +) cells (p<0.0001) and in CD8(+) cells (p = 0.03). In a subcohort of the s ame patients, Bcl-2 was significantly higher in VL- patients (n = 10) than in controls (n = 12), both in naive CD4(+) cells (p<0.0001) and in naive CD 8(+) cells (p = 0.01). Naive CD4(+) cells had higher Bcl-2 expression in VL - than in VL+ patients (p = 0.01). In a subsequent longitudinal study of ni ne HIV patients, naive CD4(+) cells increased after effective PI-HAART (p = 0.03), which paralleled an increase in Bcl-2 expression in the same cells (p = 0.02). In conclusion, upregulation of bcl-2 could be a mechanism of im mune reconstitution of naive CD4(+) T cells induced by PI-HAART.