To study the development and function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3 + CD4 + Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) β-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR β-chain was able to provide stronger TCR signals. This TCR-β-driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3 − CD4 + T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. ). The development and selection of nTreg cells in the thymus has been the subject of scientific debates for decades, and two contradicting hypotheses have been formulated. Although one hypothesis emphasized the development of nTreg cells in a T-cell receptor (TCR)-dependent manner, the other hypothesis postulated a TCR-independent mechanism. The TCR-dependent development is supported by the observation that TCR transgenic models generated from non-Treg cells did not possess any nTreg cells (7). In line with the TCR-dependent hypothesis is the notion that Treg cells developed in non-Treg TCR transgenic models only when the cognate antigen was expressed in the thymus (8-10). The TCR-independent hypothesis was proposed based on the observation that nTreg development was favored in a subset of CD4 − CD8 − double-negative (DN) cells before the expression of a full TCR on the surface, and that development of Treg cells was less affected than that of conventional CD4+ T cells in pre-TCR-α −/− (pTα) mice (11,12). Given that the pTα, together with TCR-β, is expressed as pre-TCR at the CD4 CD8 DN stage 3 (DN3) before selection at the CD4 CD8 double-positive (DP) stage, a TCR-independent Treg development was indicated. In addition, although some studies investigating the TCR repertoire of conventional T cells (Tconv) and Treg cells demonstrated a partial overlap in support of the TCR-independent hypothesis, other studies reported no gross similarity of the TCR repertoire, in line with a TCR-dependent development (13-15).TCR transgenic mice have been valuable tools in better understanding the role of T cells in health and disease. Several mouse models had been made to study the development and function of nTreg cells. First studies used existing non-Treg TCR transgenic mice and expressed the cognate antigen in the thymus...

Background: Academic stress is an important research topic due to the effect it has on the quality of life of students, future professionals and therefore, adult contributors in a society. It has been shown that students in the health field face additional stressors specific from their careers, and suffer greater stress than the general population of the same age. Methods: 52 students, 23 from Physiotherapy and 29 from Medicine programs were surveyed with Academic Stressors Academic Scale (SAS) to know academic stress level and IL-6 was quantified in serum. Results: It was found that students who perceive the academic semester as stressful “fairly often” and “many times”, increases in 50%, 75% and 76.9% during the semester; while “anxiety/distress” feeling was predominant. The most frequent SAS scale factors were “methodological deficiencies”, “student overload”, “beliefs about performance”, “lack of content value”, “participation” and “exams” Conclusions: The study revealed an IL-6 increment, and their association with “Methodological Deficiencies” at 1st moment. This study showed the importance of academic stressors identification at same time that it is a call to construct strategies to reduce stressors in University context

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immu­nodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lym­phocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diag­nosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.

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