Exploring T Cell Receptor Repertoires in Myocardial Diseases.

Mounting experimental and clinical evidence has revealed that adaptive immune mechanisms targeting myocardial antigens are triggered by different forms of cardiac injury and impact disease progression. B and T lymphocytes recognize specific antigens via unique adaptive immune receptors generated through a somatic rearrangement process that generates a potential repertoire of 1019 unique receptors. While the adaptive immune receptor repertoire diversity provides the basis for immunologic specificity, making sense of it can be a challenging task. In the present review, we discuss key aspects underlying the generation of TCRs (T cell receptors) and emerging tools for their study in the context of myocardial diseases. Moreover, we outline how exploring TCR repertoires could lead to a deeper understanding of myocardial pathophysiological principles and potentially serve as diagnostic tools.

Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children.

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

[MAbs: the history of a basic research or the curiosity as a source of wealth]. / Les anticorps monoclonaux - L'histoire d'une recherche fondamentale ou la curiosité comme source de richesse1.

In 2019, monoclonal antibodies are a worldwide annual business worth of more than 100 billions USD (i.e., about 90 billions €). In addition to their use in the clinics, monoclonal antibodies are also used for diagnosis and remain highly valuable tools for academic basic and translational research. Forty-four years after the seminal publication of Georges Köhler and César Milstein, dozens of meetings and seminars focusing on various aspects of mAbs are held annually all around the world. But forty-four years later, the scientific works and efforts that have made possible this scientific breakthrough are gradually forgotten and, for many, monoclonal antibodies are no more than a multi-million USD business alike any other big business, guided by financial markets and the results of on-going clinical trials… Time has now come for acknowledging and paying tribute to all these scientists involved in basic research, to these researchers passionate about science, some famous, some forgotten, scattered all over the world. They explored during the 20th century the frontiers of unknown and generated a knowledge that allowed the emergence of a technique that translated finally into what is one of the greatest therapeutic revolution of the modern era.

TITLE: Les anticorps monoclonaux - L'histoire d'une recherche fondamentale ou la curiosité comme source de richesse1. ABSTRACT: En 2019, les anticorps monoclonaux (Acm) vont représenter un marché mondial annuel de plus de cent milliards de dollars, soit près de 90 milliards d'euros. Outre leur utilisation en clinique, les anticorps monoclonaux sont utilisés également dans de nombreux tests diagnostiques et sont toujours des outils précieux pour la recherche fondamentale et appliquée. Quarante-quatre ans après la publication de Georges Köhler et César Milstein [1], des dizaines de congrès et séminaires de toute nature sur les anticorps monoclonaux se tiennent annuellement à travers le monde. Mais 44 ans plus tard, les travaux scientifiques qui ont amené à cette publication sont peu à peu oubliés et, dans bien des esprits, les anticorps monoclonaux ne sont qu'un business d'un multi-milliard euros/dollars comme un autre, déterminé par les marchés financiers et les résultats des derniers essais cliniques… Il est grand temps de rendre hommage à toute une génération de chercheurs fondamentalistes, à ces fous de science du xx e siècle, à ces chercheurs connus et souvent désormais méconnus, disséminés aux quatre coins du monde, qui ont exploré les frontières de l'inconnu d'alors et qui ont modelé et ciselé un savoir qui a débouché sur une technique d'obtention de molécules qui ont permis l'une des plus grandes révolutions thérapeutiques de ces vingt-cinq dernières années.