Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans

Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2low) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-γ during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response

The role of groundwater in CO₂ production and carbon storage in Mediterranean peatlands: An isotope geochemistry approach.

Peatlands are permanent wetlands recognized for ecosystem services such as biodiversity conservation and carbon storage capacity. Little information is available about their response to global change, the reason why most Earth system climate models consider a linear increase in the release of greenhouse gases (GHG), such as CO <sub>2</sub> , with increasing temperatures. Nevertheless, numerous studies suggest that an increase in the temperature may not imply a decrease in photosynthesis and carbon storage rates if water availability is sufficient, the latter being under the control of local hydrology mechanisms. Mediterranean peatlands well illustrate this fact. Since they are groundwater-dependent, they are hydrologically resilient to the strong seasonality of hydroclimatic conditions, especially during the summer drought. In the present study, we demonstrate that, even if such peatlands release CO <sub>2</sub> into the atmosphere, they can maintain a carbon storage capacity. To this end, a geochemical study disentangles the origin and fate of carbon within a Mediterranean peatland at the watershed scale. Field parameters, major ions, dissolved organic and inorganic carbon content and associated δ <sup>13</sup> C values allow for characterizing the seasonality of hydrochemical mechanisms and carbon input from an alluvial aquifer (where rain, river, shallow, and deep groundwater flows are mixing) to the peatland. The inorganic and organic content of peat soil and δ <sup>13</sup> C values of total organic matter and CO <sub>2</sub> complete the dataset, making it possible to provide arguments in favour of lower organic matter oxidation compared to primary production. Overall, this study highlights the groundwater role in the fluxes of CO <sub>2</sub> at the peatland-atmosphere interface, and more broadly the need to understand the interactions between the water and carbon cycles to build better models of the future evolution of the global climate

Introduction: spiritual landscapes of Southeast Asia

This Introduction foreshadows the main themes of this special issue on spiritual landscapes of Southeast Asia. Throughout Southeast Asia, links exist between spirit beings or potent energies and particular sites in the landscape, including trees, mountains and rivers. These are highlighted in this collection of papers via the notion of 'spiritual landscapes'. This concept also broadens anthropological approaches to the religious significance of the landscape, by problematising the separation of 'natural' and 'cultural' environments while sidestepping the implication that something called 'sacred geography' can be separated from the pragmatic activities of daily life. Following an ethnographic overview of spirit-places and environmental forces in the region, I discuss our need to take more seriously the claims of many Southeast Asian people that their landscapes have agency. In the context of religious conversion, the agency of the landscape often becomes a central concern, as reformers and missionaries seek to 'purify' the environment of such spiritual power. However, in addition to 'purification', ongoing conversion may also involve new forms of conversation with the landscape, including re-enchantments, religious syntheses or reassertions of the landscape's potency

Cerebrospinal Fluid JC Virus Antibody Index for Diagnosis of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AI(JCV)) in the diagnosis of natalizumab-associated PML. METHODS: AI(JCV) was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AI(JCV) was calculated as published. RESULTS: Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AI(JCV) > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AI(JCV) > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AI(JCV) > 1.5. INTERPRETATION: Determination of the AI(JCV) could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML

Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat

The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min−1) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters.Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min−1) increase in microvascular pressure from 11.3 ± 0.7 to 14.9 ± 0.5 mmHg and in post-capillary resistance from 7.2 ± 0.6 to 10.1 ± 1.1 mmHg ml−1. ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics.Intrasplenic ANF (6.5 pmol min−1) caused a sustained increase in intrasplenic fluid efflux from 0.1 ± 0.1 to 0.3 ± 0.1 ml min−1, and in capillary filtration coefficient (Kf) from 1.2 ± 0.5 to 2.4 ± 0.6 ml mmHg−1 min−1 (100 g tissue)−1.Mechanical elevation of splenic intravascular pressure (from 11.3 ± 0.7 to 22.4 ± 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 ± 0.3 to 1.4 ± 0.3 ml min−1).The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min−1) did not alter splenic intravascular pressure or pre-/post-capillary resistance.The ANF antagonist A71915 (8.3 and 83 pmol min−1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance.It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA