The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIV-infected individuals due to IL-7Ralpha down-regulation. Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool.
IL-7 promotes survival of resting T lymphocytes and induces T cell proliferation in lymphopenic conditions. As elevated IL-7 levels occur in HIV-infected individuals in addition to high Fas expression on T cells and increased sensitivity to Fas-induced apoptosis, we analyzed whether IL-7 has a regulatory role in Fas-mediated T cell apoptosis. We show that IL-7 up-regulates Fas expression on naive and memory T cells through a mechanism that involves translocation of Fas molecules from intracellular compartments to the cell membrane. IL-7 induced the association of Fas with the cytoskeletal component ezrin and a polarized Fas expression on the cell surface. The potential role of IL-7 in Fas up-regulation in vivo was verified in IL-7-treated macaques and in HIV-infected or chemotherapy treated patients by the correlation between serum IL-7 levels and Fas expression on T cells. IL-7 treatment primed T cells for Fas-induced apoptosis in vitro and serum IL-7 levels correlated with the sensitivity of T cells to Fas-induced apoptosis in HIV-infected individuals. Our data suggest an important role for IL-7 in Fas-mediated regulation of T cell homeostasis. Elevated IL-7 levels associated with lymphopenic conditions, including HIV-infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis.
Receptor-mediated apoptosis is proposed as an important regulator of keratinocyte homeostasis in human epidermis. We have previously reported that Fas/FasL interactions in epidermis are altered during cutaneous leishmaniasis (CL) and that keratinocyte death through apoptosis may play a pathogenic role for skin ulceration. To further investigate the alterations of apoptosis during CL, a keratinocyte cell line (HaCaT) and primary human epidermal keratinocytes were incubated with supernatants from Leishmania major-infected peripheral blood mononuclear cells. An apoptosis-specific microarray was used to assess mRNA expression in HaCaT cells exposed to supernatants derived from L. major-infected cultures. Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression were significantly up-regulated, and apoptosis was detected in both HaCaT and human epidermal keratinocyte cells. The keratinocyte apoptosis was partly inhibited through blocking of Fas or FasL and even more efficiently through TRAIL neutralization. Up-regulation of Fas on keratinocytes in epidermis and the presence of FasL-expressing macrophages and T cells in dermis were previously reported by us. In this study, keratinocytes expressing TRAIL, as well as the proapoptotic receptor TRAIL-R2, were detected in skin biopsies from CL cases. We propose that activation of Fas and TRAIL apoptosis pathways, in the presence of inflammatory mediators at the site of infection, leads to tissue destruction and ulceration during CL. (Am J
Serum IL-7 levels correlate with T-cell depletion in HIV-infected individuals. In some patients, we observed that serum IL-7 decreases upon progression to AIDS, suggesting a role for IL-7 in T-cell maintenance in sporadic cases. Interestingly, IL-7 levels were significantly lower in stable long-term non-progressors (LTNP) than in patients who lost the LTNP status in a 3-year follow-up (P < 0.001), indicating that the serum IL-7 concentration might be a valuable marker for maintenance of the LTNP state.
Purpose
To analyse and compare the number and interval of anti‐vascular endothelial growth factor (anti‐VEGF) injections in neovascular age‐related macular degeneration (nAMD), as well as the visual development in patients followed up for one to three years in clinical practice and during different index periods.
Methods
This observational study included treatment‐naïve eyes with nAMD from the Swedish Macula Register that started treatment between 2007 and 2017, stratified by different index periods (2007–2010, 2011–2013, 2014–2015 and 2016–2017) and by follow‐up cohorts for each index period of one, two or three years (cohorts 1–3). Their intravitreal anti‐VEGF treatment was assessed by number of injections, injection intervals, visual acuity (VA) and near VA change.
Results
From the earliest index period 2007–2010 to the latest 2016–2017, the number of injections increased for the comparable follow‐up time; 6.2 ± 1.4 versus 8.3 ± 2.0 injections after 1 year of treatment, 4.8 ± 1.6 versus 6.7 ± 2.4 during year 2. The last injection interval was 73 ± 34 days after 1, 71 ± 33 after 2 and 67 ± 32 after 3 years of follow‐up for the index period 2014–2015. For the same period, the percentage of eyes with at least two consecutive 12–16 weeks of injection interval over 1‐, 2‐ and 3‐year follow‐up increased from 5.2%, 15.0%, to 17.5% respectively. Baseline VA for eyes indexed 2016–2017 increased and presented with 62.1 ± 13.4 letters compared with 57.7 ± 13.5 letters in 2007–2010; p < 0.0001.
Conclusions
From the earliest to the latest index periods, the number of injections increased for the comparable follow‐up time. Accordingly, baseline VA and near VA and their outcomes improved continuously.
Interleukin-7 (IL-7) is a survival factor for naïve and memory T lymphocytes and it also increases T cell proliferation during lymphopenic conditions. Elevated levels of IL-7 have been found in the blood of HIV+ patients, which was considered as a homeostatic response to peripheral T cell depletion.We showed that HIV infection is associated with an increased proportion of IL-7Ra low/negative peripheral T lymphocytes. Down-regulation of IL-7Rα on T cells was correlated with the depletion of CD4+ T cells and also with the increased concentration of serum IL-7. The decreased IL-7Rα expression resulted in the reduced survival capacity of T cells in presence of IL-7 and was associated with low Bcl-2 expression. Mostly the memory T cells down-regulated the IL-7Rα and we found a strong association between CD28 and IL-7Rα down-regulation. Accordingly, only CD28+ T cells responded to IL-7 with strong Bcl-2 upregulation.The positive effects of IL-7 on survival and homeostatic proliferation of T cells might be severely impaired in HIVinfected individuals due to the decreased IL-7Rα expression. Chronic T cell activation may lead to an overall decrease of IL-7 mediated survival signals in HIV-infected individuals.from 2005 International Meeting of The Institute of Human Virology
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.