A5035126631- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Hematopoietic Stem Cell Transplantation
- Virus-based gene therapy research
- Viral-associated cancers and disorders
- Immunodeficiency and Autoimmune Disorders
- Herpesvirus Infections and Treatments
- Polyomavirus and related diseases
- Cancer Immunotherapy and Biomarkers
- Systemic Lupus Erythematosus Research
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- Lymphoma Diagnosis and Treatment
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Chronic Lymphocytic Leukemia Research
- Parvovirus B19 Infection Studies
- Advanced Biosensing Techniques and Applications
- Renal Transplantation Outcomes and Treatments
- Cytokine Signaling Pathways and Interactions
- Viral Infectious Diseases and Gene Expression in Insects
Nantes Université
2013-2023
Inserm
2014-2023
Université d'Angers
2017-2023
Centre National de la Recherche Scientifique
2014-2023
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers
2010-2022
Centre Hospitalier Universitaire de Nantes
1993-2018
Centre d'Investigation Clinique de Nantes
2010-2018
Établissement Français du Sang
2014-2018
Hotel Dieu Hospital
2014
Hôtel-Dieu de Paris
2013
Human V gamma 9V delta 2 T cells were shown recently to respond nonpeptidic phosphorylated molecules of mycobacterial origin (previously referred as TUBag). To investigate the early events cell activation, we have analyzed induction cytotoxicity and TNF production clones by these molecules. We showed that within minutes after exposure, TUBag induced CTL (but not expressing other TCR gamma/V or alpha/V beta regions) against a broad set target cells, including effector themselves. Induction...
Abstract The majority of peripheral blood γδ T cells in human adults expresses cell receptors (TCR) with identical V regions (Vγ9 and Vδ2). These Vγ9Vδ2 recognize the major histocompatibility complex (MHC) class I‐deficient B line Daudi broadly distributed nonpeptidic antigens present bacteria parasites. Here we show that unlike αβ or Vγ9 − cells, Vγ9Vδ2T harbor natural killer inhibitory (KIR) (mainly CD94/NKG2A heterodimers), which are known to deliver signals upon interaction MHC I...
Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed CD1+ stimulator cells. In humans, cells carrying alpha24+ homologous those expressed by NK1.1 been recently described. Here we show that these (referred as alpha24inv cells) resemble each other in several ways. First, like their counterparts, high levels TCRs can be...
Abstract Recent studies have demonstrated that a large fraction of human gamma delta PBL recognize Ag prokaryotic and eukaryotic origins, respectively found in hydrosoluble mycobacterial extracts on the Daudi Burkitt's lymphoma cells. The structural basis recognition these been presently studied detail, through analysis panel thymus- peripheral blood-derived T-cell clones. Our results suggest mycobacteria-reactive subsets are strictly overlapping hence responses against two closely related....
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing mediated metabolic changes. However, major limitation of the therapeutic application is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles cells, we have developed concept T engineered express defined γδT cell receptor (TEGs). This next generation chimeric antigen (CAR-T) not only allows for targeting hematological, but also solid tumors, therefore overcomes...
We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality this phenomenon and its relevance to autoimmunity, we studied responses CD8 from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: 5, psoriatic 4, Reiter's syndrome: 3, arthrosis: 2, uveitis: multiple sclerosis: encephalitis: 1) viral proteins...
Allelic exclusion of lymphocyte antigen receptor chains has been hypothesized as a mechanism developed by the immune system to ensure efficient repertoire selection and tight control specificity. It was effectively shown be operative for both immunoglobulin (Ig) T cell (TCR) beta chain genes. Our present observations suggest that close 1% human lymphocytes escape this allelic control, express two surface TCR with distinct superantigenic reactivities. Since high frequency dual expressors did...
CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive negative costimulatory molecules that, among other functions, control T cell motility formation of immune synapse between cells antigen-presenting (APCs). What remains incompletely understood is how CD28 leads to activation effector (Teff) but inhibition suppression by regulatory (Tregs), while PD-L1 inhibit Teff function crucial suppressive Tregs. Using alloreactive human blocking antibodies, we show here...
Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity against most infections and tumors. Natural killer (NK) are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show human NK promote cross-presentation tumor cell-derived Ag by leading Ag-specific CD8(+) activation. Surprisingly, cytotoxic function was not required. Instead, highlight a critical nonredundant role for IFN-γ TNF-α production enhance using two different...
FcγRIIIA/CD16A, the low-affinity receptor for IgG Fc portion expressed on human CD56(dim) NK cells and involved in Ab-dependent cell cytotoxicity, is shed upon activation. We found that recombinant a disintegrin metalloprotease (ADAM) 17 cleaved ectodomain of FcγRIIIA/CD16A peptide which sequence encompasses aa 191-201 stalk region but not ADAM10. MALDI-TOF analysis revealed was between Ala(195) Val(196) (i.e., 1 upstream expected position). This location cleavage site confirmed by finding...
// Christelle Retière 1 , 2, 8 Catherine Willem 1, Thierry Guillaume 3, Henri Vié Laetitia Gautreau-Rolland Emmanuel Scotet Xavier Saulquin Katia Gagne 4, Marie C. Béné 5, Berthe-Marie Imbert 6, 7, Beatrice Clemenceau Pierre Peterlin 3 Alice Garnier and Patrice Chevallier Etablissement Français du Sang, Nantes, France 2 CRCINA, INSERM, CNRS, Université d’Angers, de Hematology Department, CHU, 4 LabEx Transplantex, Strasbourg, 5...
At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful.
Knowledge of the immunodominant responses to Epstein-Barr Virus (EBV) and human cytomegalovirus (HCMV) should help generate cytotoxic T cell lines these herpesviruses. Here we report on analysis CD8 EBV HCMV in blood kidney transplant recipients undergoing viral reactivation (n = 16) healthy virus carriers 10). We used a transient COS transfection assay that permits semi-quantitative estimation CD8+ against larger number HLA / protein combinations within polyclonal thus allows rapid...
In the context of transplantation, donor and virus-specific T-lymphocyte infusions have demonstrated dramatic potential T cells as immune effectors. Unfortunately, most attempts to exploit T-cell system against nonviral malignancies in syngeneic setting been disappointing. contrast, treatments based on monoclonal antibodies (Abs) clinically successful clinical relevance several antigens therapeutic targets importance antibody-dependent cellular cytotoxicity (ADCC) pathway. present study, we...
We report herein the results we obtained and limitations experienced during production use of a bank Epstein-Barr virus (EBV)-transformed human cytotoxic T lymphocytes (EBV-CTLs). To assess feasibility toxicity this strategy, selected stored, in liquid nitrogen, 4 billion EBV-CTLs from each 13 donors. Subsequently, multicenter phase I/II study, 11 patients with EBV-associated lymphoma resistant to conventional treatments received 1–3 doses 5 million EBV-CTLs/kg 0–4 compatibilities for...
Glioblastoma multiforme (GBM) represents the most frequent and deadliest primary brain tumor. Aggressive treatment still fails to eliminate deep infiltrative highly resistant tumor cells. Human Vγ9Vδ2 T cells, major peripheral blood γδ cell subset, react against a wide array of cells represent attractive immune effector for design antitumor therapies. This study aims at providing preclinical rationale immunotherapies in GBM based on stereotaxic administration allogeneic human The feasibility...
ABSTRACT Cytotoxic T lymphocytes (CTLs) play a central role in the control of persistent human cytomegalovirus (HCMV) infection healthy virus carriers. Previous analyses specificity HCMV-reactive CD8 + CTLs drawn from vitro models which antigen-presenting cells were autologous fibroblasts infected with laboratory HCMV strains have shown focusing CTL responses against major tegument protein, pp65. By contrast, 72-kDa immediate-early protein (IE1) was identified as minor target for this...
Lymphocytes recognize antigens with highly variable heterodimeric surface receptors. Although four distinct antigen receptors could in principle be produced by any lymphocyte, only one functional combination of receptor chains has thus far been found expressed on their surface. Examination human γδ T cells revealed a population that violated this rule expressing two cell (TCRs) used different TCRγ gene alleles. Thus, current models for clonal selection may need modification, and possible...
Human memory T cells are comprised of distinct populations with different homing potential and effector functions: central that mount recall responses to Ags in secondary lymphoid organs, confer immediate protection peripheral tissues. In the present study we demonstrate a proportion express FcgammaRIIIa (CD16), perforin positive, directly mediate Ab-dependent cytotoxicity ex vivo. This particular alphabeta lymphocyte subset has morphology large granular lymphocytes, increases...
To take advantage of the large number well-characterized mouse immunoglobulins (IgGs) for study antibody-dependent cell-mediated cytotoxicity (ADCC) in human cells, we armed cytotoxic lymphocytes with a receptor Fc portion IgG antibodies. The ΝΚ-92 natural killer cell line was transduced gene (mCD16), which stably expressed on surface (referred to as NK-92 (mCD16) ). When tested against B-lymphoblastoid (BLCL) coated anti-CD20 IgG1, IgG2a or IgG2b monoclonal antibodies (mAbs), newly enabled...
Abstract Purpose: Cellular immunotherapies are currently being explored to eliminate highly invasive and chemoradioresistant glioblastoma (GBM) cells involved in rapid relapse. We recently showed that concomitant stereotactic injections of nonalloreactive allogeneic Vγ9Vδ2 T lymphocytes eradicate zoledronate-primed human GBM cells. In the present study, we investigated spontaneous reactivity toward primary cells, vitro vivo, absence any prior sensitization. Experimental Design: Through...
T-cell receptors (TCRs) are formed by stochastic gene rearrangements, theoretically generating >10 19 sequences. They selected during thymopoiesis, which releases a repertoire of about 10 8 unique TCRs per individual. How evolution shaped process that produces can effectively handle countless and evolving set infectious agents is central question immunology. The paradigm diverse enough should always provide proper, though rare, specificity for any given need. Expansion such rare T cells...
Abstract We present here a culture method for the estimation, in human blood, of number lymphocytes that can respond to mitogen by producing interleukin 2 (IL 2). T cells are cultured at limiting dilutions with PHA or Con A presence Epstein Barr virus-transformed lymphoblastoid (EB-LCL), and supernatants tested 3 days later IL content cell proliferation assay. The distribution negative wells follows expected Poisson "single-hit" relationship, suggesting assay is sensitive single type. On...