[François Gros (1925-2022)].

François Gros, a biologist by training, began his research at the Institut Pasteur. In 1961, he discovered the molecular nature of the proposed intermediary between the gene and the protein, a so-called messenger RNA (mRNA), and determined its main characteristics. The author of numerous books, François Gros has helped shape and enlightened the birth of molecular biology and the development of related biotechnologies since the 1970s.

The natural defense system and the normative self model.

Infectious agents are not the only agressors, and the immune system is not the sole defender of the organism. In an enlarged perspective, the 'normative self model' postulates that a 'natural defense system' protects man and other complex organisms against the environmental and internal hazards of life, including infections and cancers. It involves multiple error detection and correction mechanisms that confer robustness to the body at all levels of its organization.

Does a quorum sensing mechanism direct the behavior of immune cells?

Quorum sensing is a decision-making process used by decentralized groups such as colonies of bacteria to trigger a coordinated behavior. The existence of decentralized coordinated behavior has also been suggested in the immune system. In this paper, we explore the possibility for quorum sensing mechanisms in the immune response.

Systematic and systemic immunology: on the future of research and its applications.

This paper is a shortened English transcription of a lecture given on 13 February 2012 at the College de France. The lecture concluded a series of talks delivered the same year on the theme: "Immunity: the game of chance and specificity". The article comprises four parts: I.

Selfish cellular networks and the evolution of complex organisms.

Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells.

Systems medicine and integrated care to combat chronic noncommunicable diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes.

Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets.

New official nomenclature subdivides human monocytes into 3 subsets: the classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), and nonclassical (CD14(+)CD16(++)) monocytes. This introduces new challenges, as monocyte heterogeneity is mostly understood based on 2 subsets, the CD16(-) and CD16(+) monocytes. Here, we comprehensively defined the 3 circulating human monocyte subsets using microarray, flow cytometry, and cytokine production analysis.

Identification of novel functional differences in monocyte subsets using proteomic and transcriptomic methods.

Human blood monocytes can be broadly divided into two distinct subsets: CD14+CD16- and CD14+/lowCD16+ subsets. Perturbation in their proportions in the blood has been observed in several disease conditions. Although numerous phenotypic and functional differences between the two subsets have already been described, the roles contributed by each subset during homeostasis or disease conditions are still largely unclear.

IL-1beta, IL-6, and RANTES as biomarkers of Chikungunya severity.

Background: Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity.

Methods And Findings: Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study.

Many human peripheral VH5-expressing IgM+ B cells display a unique heavy-chain rearrangement.

The immunoscope methodology has proven useful to analyze T-cell repertoires in mice and humans. We adapted it to the analysis of VH chains of human peripheral B cells by setting up a quantification of various VH and JH segments and the profiling of IgM-, IgG-, IgA- and IgE-expressing B cells. We then tested the hypothesis that the human B-cell and T-cell repertoires have a similar diversity of VH and V-beta rearrangements.

T cell repertoire diversity is required for relapses in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.

Comparison of TCRalphabeta repertoires of myelin oligodendrocyte glycoprotein (MOG)-specific T lymphocytes in C57BL/6 and TdT-deficient littermates (TdT(-/-)) generated during experimental autoimmune encephalomyelitis (EAE) highlights a link between a diversified TCRalphabeta repertoire and EAE relapses. At the onset of the disease, the EAE-severity is identical in TdT(+/-) and TdT(-/-) mice and the neuropathologic public MOG-specific T cell repertoires express closely similar public Valpha-Jalpha and Vbeta-Jbeta rearrangements in both strains. However, whereas TdT(+/+) and TdT(+/-) mice undergo successive EAE relapses, TdT(-/-) mice recover definitively and the lack of relapses does not stem from dominant regulatory mechanisms.

Lineage relationships, homeostasis, and recall capacities of central- and effector-memory CD8 T cells in vivo.

The lineage relationships of central-memory T cells (T(CM)) cells and effector-memory T cells (T(EM)), as well as their homeostasis and recall capacities, are still controversial. We investigated these issues in a murine model using two complementary approaches: T cell receptor repertoire analysis and adoptive transfer experiments of purified H-Y-specific T(CM) and T(EM) populations. Repertoire studies showed that approximately two thirds of T(CM) and T(EM) clones derived from a common naive precursor, whereas the other third was distinct.

Valpha and Vbeta public repertoires are highly conserved in terminal deoxynucleotidyl transferase-deficient mice.

T cell repertoires observed in response to immunodominant and subdominant peptides include private, i.e., specific for each individual, as well as public, i.

Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells.

Dominant tolerance is mediated by regulatory T cells (T(reg)) that control harmful autoimmune T cells in the periphery. In this study, we investigate the implication of T(reg) in modulating infiltrating T lymphocytes in human metastatic melanoma. We found that CD4(+)CD25(high) T cells are overrepresented in metastatic lymph nodes (LNs) with a 2-fold increased frequency compared with both tumor-free LNs and autologous PBMCs.

The intratumoral application of poly-G-oligodeoxynucleotides does not augment the naturally induced antitumoral CD8-T-cell response in P815 mastocytomas.

DNA sequences containing CpG have been described to induce a strong immune reaction by acting on a variety of immune cells including a strong and pronounced antitumoral response. Poly-G-oligodeoxynucleotides (ODNs) on the other hand have been attributed the preferential induction of CD8-T-cell proliferation when used in vitro. This activity led us to the investigation of the possible antitumoral properties of poly-G-ODNs in an established CD8-dependent tumor eradication model.

Follow-up of the T-cell clonality in Sezary patients treated by extracorporeal photopheresis using a new assay: the immunoscope technique.

Sezary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4+ T-cells. Extracorporeal photochemotherapy (ECP) may induce a transient improvement of the clinical signs but it's efficiency is discussed. In order to investigate the T-cell clonality in the peripheral blood of patients with Sezary syndrome and to monitor its evolution in 8 patients treated by ECP, we used the Immunoscope technique.

The repertoires of circulating human CD8(+) central and effector memory T cell subsets are largely distinct.

Memory T cells are divided into central and effector subsets with distinct functions and homing capabilities. We analyzed the composition and dynamics of the CD8(+) T cell repertoire of these subsets within the peripheral blood of four healthy individuals. Both subsets had largely distinct and autonomous TCRbeta repertoires.

Extrathymic T cell lymphopoiesis: ontogeny and contribution to gut intraepithelial lymphocytes in athymic and euthymic mice.

In the absence of thymopoiesis, T lymphocytes are nevertheless present, mainly in the gut epithelium. Ontogeny of the extrathymic pathway and the extent of its involvement in euthymic mice are controversial. These questions have been addressed by assessing the expression of recombinase activating gene (RAG) through the use of green fluorescent protein RAG2 transgenic mouse models.

Mutational analysis and molecular modeling of the binding of Staphylococcus aureus enterotoxin C2 to a murine T cell receptor Vbeta10 chain.

We investigated the role of the beta chain HV4 region in the binding of a Vbeta10 T cell receptor to superantigen S. aureus enterotoxin C2 (SEC2)/MHC class II complexes. Residues 6971 of the Cw3/1.

A prospective study on the evolution of the T-cell repertoire in patients with Sézary syndrome treated by extracorporeal photopheresis.

Sézary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4(+) T cells. Extracorporeal photochemotherapy may induce a transient improvement of the clinical signs, but its efficiency is discussed. To investigate the frequency of the T-cell clone in the peripheral blood of patients with Sézary syndrome and to monitor its evolution in patients treated using extracorporeal photopheresis or chemotherapy, we used the immunoscope technique.

T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation.

Granuloma annulare is a common granulomatous infiltration of the skin of unknown etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and could find in all patients significant numbers of CD4-T cells. These cells showed a broad usage of the different T cell receptor Vbeta families and a rather unbiased repertoire when the complementary determining region 3 spectra were analyzed by the Immunoscope technique.

Combination of MHC-peptide multimer-based T cell sorting with the Immunoscope permits sensitive ex vivo quantitation and follow-up of human CD8+ T cell immune responses.

Identification of MHC-restricted antigens and progress in the induction and control of adaptive cytotoxic immune responses have led to renewed interest in immunotherapy as a treatment for severe pathologies such as cancer and autoimmune diseases. Reliable procedures for detecting and monitoring T cell responses induced by the treatment throughout a clinical trial are needed in order to design rational protocols with increased efficiency. We have attempted to develop such a procedure by combining T cell sorting using HLA-peptide complexes multimerized on magnetic beads together with the quantitative Immunoscope approach.