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We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies and T-cell responses against SARS-CoV-2 and human coronavirus (HCoV) 229E and OC43 in 11 SARS-CoV-2 serodiscordant couples in Strausbourg, France, in which 1 partner had evidence of mild coronavirus disease (COVID-19) and in 10 unexposed healthy controls. Patients with confirmed COVID-19 were considered index patients and their partners close contacts. All index patients displayed positive SARS-CoV-2-specific antibody and T-cell responses that lasted up to 102 days after symptom onset. All contacts remained seronegative for SARS-CoV-2; however, 6 reported COVID-19 symptoms within a median of 7 days after their partners, and 4 of those showed a positive SARS-CoV-2-specific T-cell response against 3 or 4 SARS-CoV-2 antigens that lasted up to 93 days after symptom onset. The 11 couples and controls displayed positive T-cell responses against HCoV-229E or HCoV-OC43. These data suggest that exposure to SARS-CoV-2 can induce virus-specific T-cell responses without seroconversion.

Background: Sepsis is the leading cause of mortality for critically ill patients worldwide. Patients develop T lymphocyte dysfunctions leading to T-cell exhaustion associated with increased risk of death. As interleukin-7 (IL-7) is currently tested in clinical trials to reverse these dysfunctions, it is important to evaluate the expression of its specific CD127 receptor on the T-cell surface of patients with septic shock. Moreover, the CD127 low PD-1 high phenotype has been proposed as a T-cell exhaustion marker in chronic viral infections but has never been evaluated in sepsis. The objective of this study was first to evaluate CD127 and CD127 low PD-1 high phenotype in septic shock in parallel with functional T-cell alterations. Second, we aimed to reproduce septic shock-induced T-cell alterations in an ex vivo model., Methods: CD127 expression was followed at the protein and mRNA levels in patients with septic shock and healthy volunteers. CD127 low PD-1 high phenotype was also evaluated in parallel with T-cell functional alterations after ex vivo activation. To reproduce T-cell alterations observed in patients, purified T cells from healthy volunteers were activated ex vivo and their phenotype and function were evaluated., Results: In patients, neither CD127 expression nor its corresponding mRNA transcript level was modified compared with normal values. However, the percentage of CD127 low PD-1 high T cells was increased while T cells also presented functional alterations. CD127 low PD-1 high T cells co-expressed HLA-DR, an activation marker, suggesting a role for T-cell activation in the development of this phenotype. Indeed, T-cell receptor (TCR) activation of normal T lymphocytes ex vivo reproduced the increase of CD127 low PD-1 high T cells and functional alterations following a second stimulation, as observed in patients. Finally, in this model, as observed in patients, IL-7 could improve T-cell proliferation., Conclusions: The proportion of CD127 low PD-1 high T cells in patients was increased compared with healthy volunteers, although no global CD127 regulation was observed. Our results suggest that TCR activation participates in the occurrence of this T-cell population and in the development of T-cell alterations in septic shock. Furthermore, we provide an ex vivo model for the investigation of the pathophysiology of sepsis-induced T-cell immunosuppression and the testing of innovative immunostimulant treatments.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) hold its eighth practice harmonization workshops on September 2017. In a workshop dedicated to chimeric antigen receptor T-cell therapy (CAR T-cells), the society issued recommendations regarding the prerequisite for hematopoietic cellular therapy programs to set up CAR T-cell therapy. In this article we focused on the prerequisite needed, in France, for a hematopoietic transplantation unit to start a CAR T-cell program with industrial manufactured cells within investigational products or after market access authorization., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The tyrosine kinase 2 variant rs34536443 has been established as a genetic risk factor for multiple sclerosis in a variety of populations. However, the functional effect of this variant on disease pathogenesis remains unclear. This study replicated the genetic association of tyrosine kinase 2 with multiple sclerosis in a cohort of 1366 French patients and 1802 controls. Furthermore, we assessed the functional consequences of this polymorphism on human T lymphocytes by comparing the reactivity and cytokine profile of T lymphocytes isolated from individuals expressing the protective TYK2(GC) genotype with the disease-associated TYK2(GG) genotype. Our results demonstrate that the protective C allele infers decreased tyrosine kinase 2 activity, and this reduction of activity is associated with a shift in the cytokine profile favouring the secretion of Th2 cytokines. These findings suggest that the rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. This impact of tyrosine kinase 2 on effector differentiation is likely to be of wider importance because other autoimmune diseases also have been associated with polymorphisms within tyrosine kinase 2. The modulation of tyrosine kinase 2 activity might therefore represent a new therapeutic approach for the treatment of autoimmune diseases.