Cross-Reactivity of Herpesvirus-Specific CD8 T Cell Lines Toward Allogeneic Class I MHC Molecules

Although association between persistent viral infection and allograft rejection is well characterized, few examples of T-cell cross-reactivity between self-MHC/viral and allogeneic HLA molecules have been documented so far. We appraised in this study the alloreactivity of CD8 T cell lines specific for immunodominant epitopes from human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). CD8 T cell lines were generated after sorting with immunomagnetic beads coated with either pp65495–503/A*0201, BMLF1259–267/A*0201, or BZLF154–64/B*3501 multimeric complexes. Alloreactivity of the CD8 T cell lines against allogeneic class I MHC alleles was assessed by screening of (i) TNF-α production against COS-7 cells transfected with as many as 39 individual HLA class I-encoding cDNA, and (ii) cytotoxicity activity toward a large panel of HLA-typed EBV-transformed B lymphoblastoid cell lines. We identified several cross-reactive pp65/A*0201-specific T cell lines toward allogeneic HLA-A*3001, A*3101, or A*3201. Moreover, we described here cross-recognition of HLA-Cw*0602 by BZLF1/B*3501-specific T cells. It is noteworthy that these alloreactive CD8 T cell lines showed efficient recognition of endothelial cells expressing the relevant HLA class I allele, with high level TNF-α production and cytotoxicity activity. Taken together, our data support the notion that herpes virus-specific T cells recognizing allo-HLA alleles may promote solid organ rejection

Zoning, land use and real estate values : an econometric approac

International audienc

Between environmental protection and urban development: How changes in land use planning affect coastal land markets in Aquitaine, France

This article proposes an analysis of actual land use planning policies on coastal Aquitaine, with a focus on the area of Bassin dArcachon. We first match zoning changes between 2001 and 2010 with land use changes. New development zones and a rise inprotection of "natural" uses are the main observed tendencies. Second, we link theses evolutions to land market dynamics. Time spent between buying and constructing suggests the existence of speculative behaviours. Moreover, we test whether changes in zoning produce externalities that are capitalized in land values. Our results show that potential urbanisation zones generate a price premium, but it is not the case for new "natural" zones

Using α radiation to boost cancer immunity?

Radioimmunotherapy delivers radiation directly to cancer cells by the mean of a tumor specific vector coupled to a radionuclide. Alpha radionuclides are very potent agents to treat disseminated cancer and metastasis. The demonstration that alpha radiation can also induce immunogenic cell death reinforces the interest of their clinical development.JRC.E.5-Nuclear chemistr

Tolerancing and characterization of curved image sensor systems

International audienceCurved image sensors, not having to correct the field curvature, are considered a relevant solution for improving the vast majority of optical systems. They offer the possibility of designing compact aberration-free optical systems. In this work, we explain the advantage of the curved sensor system using the aberration theory. A complete procedure was developed to produce functional curved sensors and functional prototypes were carried out. This paper focuses on the tolerancing process of curved sensors and its inclusion in optical design. A compact objective prototype designed and produced demonstrates the advantage of curvature and the impact of tolerancing

Comparative analysis of multiple myeloma treatment by CD138 antigen targeting with bismuth-213 and Melphalan chemotherapy.

Multiple myeloma (MM) is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow. Despite intense research to develop new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) has been shown to be effective in vivo in a MM model. In order to define where alpha-RIT stands in MM treatment, the aim of this study was to compare Melphalan, MM standard treatment, with alpha-RIT using a [213Bi]-anti-mCD138 antibody in a syngeneic mouse MM model. Methods: C57BL/KaLwRij mice were grafted with 1x106 5T33 murine MM cells. Luciferase transfected 5T33 were used for in vivo localization. The first step of the study was to assess the dose-response of Melphalan 21 days after engrafment. The second step consisted in therapeutic association: Melphalan followed by RIT at Day 22 and Day 25 after engraftment. Toxicity (animal weight, blood cell counts) and treatment efficacy were studied in animals receiving no treatment, injected with Melphalan alone, RIT alone at Day 22 and Day 25 (3.7MBq of [213Bi]-anti-CD138) and Melphalan combined with alpha-RIT. Results: Fifty percent of untreated mice died by Day 63 after MM engraftment. In mice treated with Melphalan alone, only the 200 μg dose improved median survival. No animal was cured after Melphalan treatment whereas 60% of the mice survived with RIT alone at Day 22 after tumor engrafment with only slight and reversible haematological radiotoxicity. No effect was observed with alpha-RIT 25 days after engraftment. Melphalan and alpha-RIT association does not improve overall survival compared to RIT alone, and results in increased leukocyte and red blood cell toxicity. Conclusions: Alpha-RIT seems to be a good alternative to Melphalan. Association of these two treatments provides no benefit. The perspectives of this work would be to evaluate RIT impact in the regimens incorporating the novel agents bortezomide, thalidomide and lenalidomide.JRC.E.5-Nuclear chemistr

213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

Radioimmunotherapy (RIT) with beta-emetting emitting radionuclides is a promising treatment in lymphoma. Though However, the efficiency of beta-emitting radionuclides to kill isolated tumor cells is limited by the relatively long range of beta radiation in human tissue, resulting in deposition of most of the beta particle energy far from the targeted cell. For disease such as leukemia and for residual disease, the use of alpha emitters which deliver large amounts of energy (several MeV) in an area of less than 100 µm has been developed. Alpha emitting radionuclides such as 213Bi or 211At have short half-lives and therefore require a rapid targeting of the tumor. In this context, alpha RIT appears as a particularly attractive therapy in multiple myeloma (MM). Indeed, in MM since the marrow shows diffuse or focal radiosensitive plasma cells involvement, the use of a specific vector coupled with high energy particles such as alpha shall enable localized destruction of myeloma cells with limited damages to surrounding healthy tissues. Syndecan-1 (CD138), a heparan sulfate proteoglycan, is constantly expressed on tumor cells in MM. Therefore this surface antigen is an attractive candidate for targeted therapy. The aim of the study was to assess toxicity and efficacy of RIT using 213Bi-anti-mCD138 in a murine MM model. The model was obtained using the 5T33 line that spontaneously occurred in C57BL/KaLwRij mice and has been propagated in vivo by intravenous transfer into young syngeneic recipients. Mice were treated using 213Bi-anti-mCD138 at 4 injected activities (1.85, 3.7, 7.4 and 11.1 MBq). Groups treated with 3.7 and 7.4 MBq exhibited a median survival above 300 days and 227 days respectively compared to 45.5 days in control group. The highest activity (11.1 MBq) was rapidly toxic while the lowest activity (1.85 MBq) gave results similar to the control. With activities of 3.7 and 7.4 MBq, surviving mice exhibit a transient hematological toxicity and we observed at 7.4 MBq only, a temporary sign of low myelotoxicity. This study demonstrated excellent therapeutic efficacy of 213Bi-anti-mCD138 RIT in MM.JRC.E.5-Nuclear chemistr