ObjectiveIn multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8+ T cells. These clones have been assumed – but never demonstrated – to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8+ T cells in the disease.MethodsFor the first time, TCR Vβ repertoire from paired blood (purified CD8+ and CD4+ T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8+ T cells were characterized by fluorescent staining.ResultsTCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8+ T cells. In parallel, we showed that blood oligoclonal CD8+ T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B.InterpretationThis study highlights the predominant implication of CD8+ T cells in MS pathophysiology and demonstrates that potentially aggressive CD8+ T cells can be easily identified and characterized from blood and CSF samples.

Objectives To conduct a model-driven meta-analysis of correlational research on psychological and motivational predictors of diabetes outcomes, with adherence factors as mediators. Methods A comprehensive literature search of published and unpublished studies located a sample of 775 individual correlational or predictive studies reported across 739 research reports. Results Results varied according to the outcome variable included in the regression models. Depression had a larger negative effect on adherence to physical activity than on dietary adherence. Coping and self-efficacy were strongly related to dietary adherence, which was strongly related to improved glycemic control. Medication adherence was related to glycosylated hemoglobin, whereas medications and self-monitoring were related to fasting blood glucose. Adding appointment keeping to the models did not significantly alter the results. Conclusion Self-efficacy was the most consistent predictor of all adherence behaviors and dietary adherence was the most significant predictor of HbA1c. Physical activity was the most predictive factor of BMI and glucose self-monitoring the most predictive of FBG. Practice implications Metabolic control is a primary goal in T2DM, so the best pathway to attaining that goal appears to be an emphasis on self-efficacy and dietary adherence.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by focal demyelination patches associated with inflammatory infiltrates containing T lymphocytes. For decades, CD4+ T cells have been recognized as playing a major role in the disease, especially in animal models, which has led to the development of several therapies. However, interest has recently developed in the involvement of CD8+ T cells in MS following the analysis of infiltrating T cells in human brain lesions. A broad range of evidence now suggests that the pathological role of this T cell subset in MS may have been underestimated. In this review, we summarize the literature implicating CD8+ T cells in the pathophysiology of MS. We present data from studies in the fields of genetics, anatomopathology and immunology, mainly in humans but also in animal models of MS. Altogether, this strongly suggests that CD8+ T cells may be major effectors in the disease process, and that the development of treatments specifically targeting this subset would be germane.