Low-Dose IL-2 Reduces Lymphocyte Apoptosis and Increases Naive CD4 Cells in HIV-1 Patients Treated with HAART

Exogenous Interleukin-2 Administration Corrects the Cell Cycle Perturbation of Lymphocytes from Human Immunodeficiency Virus-Infected Individuals

“…Interestingly, a recent report by Kovacs and colleagues indicates that IL-2 therapy also induces an increased expression of its receptor, CD25, on CD4 ϩ T cells (32a), perhaps suggesting a role for exogenous IL-2 in increasing the T-cell responsiveness to suboptimal levels of endogenous cytokine. However, in the clinical setting it is difficult to assess if there is an additional in vivo antiapoptotic effect of IL-2 as opposed to highly active antiretroviral therapy (HAART) alone (2,5,13,46), given the fact that HAART itself induces a striking reduction of the HIV-induced hyperimmune activation and apoptosis (4,7,29). It is therefore still difficult, at this time, to determine to what extent the intrinsic defect of the endogenous IL-2 autocrine and paracrine function is directly responsible in vivo for the observed cell cycle perturbation.…”

IL-7 is a potent and proviral strain–specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART

“…1G5 cells (2 × 10 6 cells/ml maintained in RPMI-1640 media supplemented with 10% fetal bovine serum) were treated with various concentrations of IL-7 (10-100 ng/ml). Cells were collected at different time points (6,24, and 48 hours after addition of IL-7), lysed in 100 μl of reporter lysis buffer (BD Biosciences -Pharmingen), and assayed for luciferase activity by using commercially available reagents (BD Biosciences -Pharmingen) with a FB12 Luminometer (Zylux Corp.). The effects of PHA (10 ng/ml), PMA (10 ng/ml), and IL-2 (10 ng/ml) were also analyzed separately in these assays.…”

“…Several cytokines, including IL-2, IL-7, and IL-15, which share a common γ chain, might have putative roles in improving control of HIV-1 infection; of these, IL-2 is the best characterized (2)(3)(4). Although recombinant human IL-2 (rhIL-2) plus HAART produced significant CD4 + T lymphocyte expansion without an increase in viral load (5)(6)(7)(8), the effects of this combination on purging viral reservoirs is somewhat unclear (2,3).…”

Biochemical mechanisms of HIV induced T cell apoptosis

“…In fact, Pandolfi et al reported that intermittent low dose IL-2 with HAART decreased spontaneous apoptosis and increased the number of CD4 + T cells. 100 Other studies have shown that anti-retroviral drugs given with IL-2 significantly elevated CD45RO and CD45RA cell numbers and decreased plasma viral load. 97,101 In addition, CD45RA cells recovered the ability to produce IL-2, IL-4 and IFN-gamma in vitro, suggesting that treated individuals might have an improved immune response.…”