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Diani M.,tituto Ortopedico Galeazzi | Diani M.,University of Milan | Altomare G.,tituto Ortopedico Galeazzi | Altomare G.,University of Milan | Reali E.,Laboratory of Translational Immunology
Autoimmunity Reviews | Year: 2015

According to the current view the histological features of psoriasis arise as a consequence of the interplay between T cells, dendritic cells and keratinocytes giving rise to a self-perpetuating loop that amplifies and sustains inflammation in lesional skin. In particular, myeloid dendritic cell secretion of IL-23 and IL-12 activates IL-17-producing T cells, Th22 and Th1 cells, leading to the production of inflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines mediate effects on keratinocytes thus establishing the inflammatory loop.Unlike psoriasis the immunopathogenic features of psoriatic arthritis are poorly characterized and there is a gap in the knowledge of the pathogenic link between inflammatory T cell responses arising in the skin and the development of joint inflammation.Here we review the knowledge accumulated over the years from the early evidence of autoreactive CD8 T cells that was studied mainly in the years 1990s and 2000s to the recent findings of the role of Th17, Tc17 cells and γδ T cells in psoriatic disease pathogenesis. The review will also focus on common and distinguishing features of T cell responses in psoriatic plaques and in synovial fluid of patients with psoriatic arthritis.The integration of this information could help to distinguish the role played by T cells in the initiation phase of the disease from the role of T cells as downstream effectors sustaining inflammation in psoriatic plaques and potentially leading to disease manifestation in distant joints. © 2014 Elsevier B.V. Source

Sforza F.,University of Ferrara | Nicoli F.,University of Ferrara | Gallerani E.,University of Ferrara | Finessi V.,University of Ferrara | And 5 more authors.
AIDS | Year: 2014

OBJECTIVE:: HIV infection is characterized by several immune dysfunctions of both CD8 and CD4 T cells as hyperactivation, impairment of functionality and expansion of memory T cells. CD8 T-cell dysfunctions have been associated with increased expression of T-bet, Eomesdermin and pro-inflammatory cytokines, and with down-regulation of CD127. The HIV-1 trans-activator of transcription (Tat) protein, which is released by infected cells and detected in tissues of HIV-positive individuals, is known to contribute to the dysregulation of CD4 T cells; however, its effects on CD8 T cells have not been investigated. Thus, in this study, we sought to address whether Tat may affect CD8 T-cell functionality and programming. METHODS:: CD8 T cells were activated by T-cell receptor engagement in the presence or absence of Tat. Cytokine production, killing capacity, surface phenotype and expression of transcription factors important for T-cell programming were evaluated. RESULTS:: Tat favors the secretion of interleukin-2, interferon-γ and granzyme B in CD8 T cells. Behind this functional modulation we observed that Tat increases the expression of T-bet, Eomesdermin, Blimp-1, Bcl-6 and Bcl-2 in activated but not in unstimulated CD8 T lymphocytes. This effect is associated with the down-regulation of CD127 and the up-regulation of CD27. CONCLUSION:: Tat deeply alters the programming and functionality of CD8 T lymphocytes. © 2014 Lippincott Williams and Wilkins. Source

Kranendonk M.E.G.,University Utrecht | Kranendonk M.E.G.,Molecular Cancer Research | Visseren F.L.J.,University Utrecht | Van Herwaarden J.A.,UMC Utrecht | And 4 more authors.
Obesity | Year: 2014

Objective: Insulin resistance (IR) is a key mechanism in obesity-induced cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT) contributes to systemic IR, the effect of human AT-extracellular vesicles (EVs) on insulin signaling in liver and muscle cells was determined. Methods: EVs released from human subcutaneous (SAT) and omental AT (OAT)-explants ex vivo were used for stimulation of hepatocytes and myotubes in vitro. Subsequently, insulin-induced Akt phosphorylation and expression of gluconeogenic genes (G6P, PEPCK) was determined. AT-EV adipokine levels were measured by multiplex immunoassay, and AT-EVs were quantified by high-resolution flow cytometry. Results: In hepatocytes, AT-EVs from the majority of patients inhibited insulin-induced Akt phosphorylation, while EVs from some patients stimulated insulin-induced Akt phosphorylation. In myotubes AT-EVs exerted an ambiguous effect on insulin signaling. Hepatic Akt phosphorylation related negatively to G6P-expression by both SAT-EVs (r= -0.60, P=0.01) and OAT-EVs (r= -0.74, P=0.001). MCP-1, IL-6, and MIF concentrations were higher in OAT-EVs compared to SAT-EVs and differently related to lower Akt phosphorylation in hepatocytes. Finally, the number of OAT-EVs correlated positively with liver enzymes indicative for liver dysfunction. Conclusions: Human AT-EVs can stimulate or inhibit insulin signaling in hepatocytes- possibly depending on their adipokine content- and may thereby contribute to systemic IR. © 2014 The Obesity Society. Source

Geneugelijk K.,Laboratory of Translational Immunology | Spierings E.,Laboratory of Translational Immunology
Cytotherapy | Year: 2015

Hematopoietic stem cell transplantation is currently used as a curative treatment for patients with malignant and non-malignant hematologic diseases. Human leukocyte antigen (HLA) matching is a major determinant for hematopoietic stem cell transplantation outcome. For patients lacking a fully HLA-matched donor, umbilical cord blood (UCB) units are alternative sources of hematopoietic stem cells because UCB transplantation allows a less stringent HLA matching. However, selection of the optimal UCB units remains challenging. The current UCB donor selection strategies are based on both cell dose and HLA matching. This Review focuses on the immunogenetic factors that influence UCB donor selection and highlights the future perspectives in UCB donor search. © 2015 International Society for Cellular Therapy. Source

Gerritsen B.,University Utrecht | Pandit A.,University Utrecht | Pandit A.,Laboratory of Translational Immunology
Immunology and Cell Biology | Year: 2016

CD8+ T cells have an important role in protection against infections and reinfections of intra-cellular pathogens like viruses. Naive CD8+ T cells circulating in blood or lymphoid tissues can get activated upon stimulation by cognate antigen. The activated T cells undergo rapid proliferation and can expand more than 10 4 -folds comprising largely of effector T cells. Upon antigen clearance, the CD8+ T-cell population contracts due to apoptosis, leaving behind a small population of memory T cells. The timing and mechanisms underlying the differentiation of naive cells into effector cells and memory cells is not yet clear. In this article, we review the recent quantitative studies that support different hypotheses of CD8+ T-cell differentiation. © 2016 Australasian Society for Immunology Inc. All rights reserved. Source

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