Naive CD4 + T Lymphocytes Express High Levels of Bcl-2 after Highly Active Antiretroviral Therapy for HIV Infection

Abstract

The mechanism causing the increasing number of peripheral T cells after highly active antiretroviral therapy (HAART) is still unclear. The bcl-2 oncogene prevents spontaneous apoptosis (SA) in lymphocytes. Spontaneous apoptosis could be a determinant of HIV immunodeficiency and can be reversed by HAART 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 with efficacy of PIHAART. Forty-nine HIV⁺ patients (cases) and 26 HIV^- individuals (controls) were evaluated. Patients receiving PI-HAART, and who had undetectable 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 controls in CD8⁺ cells (p = 0.02), but not in CD4⁺ cells (p > 0.05). Interestingly, 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 same 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 CD8⁺ 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 nine 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 immune reconstitution of naive CD4⁺ T cells induced by PI-HAART.