Granulocyte Colony‐Stimulating Factor Increases CD4⁺T Cell Counts of Human Immunodeficiency Virus–Infected Patients Receiving Stable, Highly Active Antiretroviral Therapy: Results from a Randomized, Placebo‐Controlled Trial

Abstract

Thirty human immunodeficiency virus (HIV)-infected patients with CD4+ T cell counts <350 cells/mm3 who had received stable, highly active antiretroviral therapy (HAART) for at least 24 weeks were randomized to receive either placebo or granulocyte colony-stimulating factor (G-CSF; 0.3 mg/mL 3 times a week) for 12 weeks. Blood samples were collected at specified time points. G-CSF treatment enhanced the total lymphocyte count (P=.002) and increased CD3+ (P=.005), CD4+ (P=.03), and CD8+ (P=.004) T cell counts as well as numbers of CD3-CD16+CD56+ NK cells (P=.001). The increases in CD4+ and CD8+ cell counts resulted from increases in CD45RO+ memory T cells and cells expressing the CD38 activation marker. Lymphocyte proliferative responses to phytohemagglutinin and Candida antigen decreased, whereas NK cell activity and plasma HIV RNA did not change during G-CSF treatment. After 24 weeks, all immune parameters had returned to baseline values. This study suggests that G-CSF treatment of HIV-infected patients receiving stable HAART increases the concentration of CD4+, CD8+, and NK cells without inducing changes in the virus load.

Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4 + T lymphocytes

“…Moreover, HIV antigen acquisition from live cells by DC could be an efficient mechanism to induce recognition of very low amounts of viral proteins and destruction of latent viral reservoirs. This mechanism could probably be enhanced by using either granulocyte colony-stimulating factor to promote limited viral production in resting T lymphocytes and macrophages (44,45), or IL-2 to promote viral production in T cells and restore T cell help (46,47), combined with IFN␣ to enhance crosspresentation, and CD4 ϩ T helper 1 and CD8 ϩ T cell effector functions (48,49), during highly active antiretroviral treatmentstructured interruptions. Thus, eradication of reservoirs might be obtained.…”

T‐Cell Mean Telomere Lengths Changes in Treatment Naïve HIV‐Infected Patients Randomized to G‐CSF or Placebo Simultaneously with Initiation of HAART

“…Our previous report on similar CD4 + T‐cell increases but greater risk of virological failure in HIV‐infected individuals treated with G‐CSF and HAART may simultaneously seem to suggest that the lymphocyte function is unaffected by the addition of G‐CSF when initiating HAART [9]. However, we previously reported a reduced lymphocyte proliferative response and increased numbers of memory T cells in a group of G‐CSF treated HIV‐infected patients [11] in contrast to the recruitment of neutrophil cells mediated by G‐CSF [12]. In this study we use the mean TRF length as an indicator of the replicative history of CD4 + and CD8 + T cells.…”

Effects of G‐CSF on Telomere Lengths in PBMCs from Human Immunodeficiency Virus‐Infected Patients: Results From a Randomized, Placebo‐Controlled Trial

“…However, 12 weeks after discontinuation of G-CSF, the number of PBMC and percentages of lymphocytes and monocytes had returned to baseline values ( Table 1). Concentrations of CD4 T cells increased signi®cantly in response to treatment with G-CSF (236 6 90 cells/mm 3 to 307 6 138 cells/mm 3 ; P 0.03) [8]. The increased CD4 T-cell count resulted from an increase in the number of memory CD4 CD45RO T cells (72.3 6 44.3 cells/mm 3 to 95.5 6 63.2 cells/mm 3 ; P 0.04) [8].…”

“…Concentrations of CD4 T cells increased signi®cantly in response to treatment with G-CSF (236 6 90 cells/mm 3 to 307 6 138 cells/mm 3 ; P 0.03) [8]. The increased CD4 T-cell count resulted from an increase in the number of memory CD4 CD45RO T cells (72.3 6 44.3 cells/mm 3 to 95.5 6 63.2 cells/mm 3 ; P 0.04) [8]. However, there were no signi®cant changes in naõ Ève CD4 CD45RA T-cell population.…”