Effects of Subcutaneous IL‐2 Therapy on Telomere Lengths in PBMC in HIV‐Infected Patients

Abstract

In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)-infected individuals were included and IL-2 was administered subcutaneously with 3 Â 10 6 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P 0.03) and 286 bp at week 8 (P 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naõ Ève and memory phenotype within both CD4 1 and CD8 1 cells. This study shows that IL-2 treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected individuals, indicating that IL-2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

“…8 The coexistence of enhanced myelopoiesis (as revealed by increased PMN counts) and defects in T cell counts favors the hypothesis that IL-2 and GM-CSF expand post-PBSCT myelopoiesis at the expense of T cell regeneration through a mechanism of in vivo stem cell competition. Additionally, a recent report by Aladdin et al 33 showed that subcutaneous IL-2 administration shortens telomere length of peripheral blood mononuclear cells of individuals infected with HIV with selective expansion of memory T cells and concomitant reduction of both CD4 ϩ CD45RA ϩ and CD8 ϩ CD45RA ϩ naive lymphocytes, which is highly reminiscent of our present observations. Finally, the small size of our patient sample, the short follow up of G-CSF/EPO plus IL-2 series and the lack of relevant differences in the rate of early and late relapse between our distinct patient series prevent any preliminary conclusion on the clinical role of post-PBSCT IL-2 addition to G-CSF/EPO regimen.…”

Manipulating both the inhibitory and stimulatory immune system towards the success of therapeutic vaccination against chronic viral infections

“…IL-2 administration increased the number of LCMV-specific CD8 1 T cells and resulted in decreased viral burden, indicating therapeutic potential of IL-2 for chronic viral infections. In addition, many clinical trials of IL-2 administration in HIVinfected patients have been performed, although the main purpose of these trials is to maintain or increase CD4 1 T-cell numbers rather than expand virus-specific CD8 1 T-cell numbers (195)(196)(197)(198). Through these trials, IL-2 therapy was shown to significantly increase and sustain CD4 1 T-cell counts in a large majority of patients compared with patients who are treated with antiretroviral drugs alone ( Table 2).…”