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Petrographic analysis of 49 sediments and 63 Neolithic ceramics from eight sites of Estremadura and six sites of the Algarve of central and southern Portugal, respectively, discerned distinct production technologies for each area. Raw materials available near archaeological sites were utilized. Fabrics that do not correspond to regionally available materials, however, indicate imports or migration. This suggests the existence of bidirectional maritime routes rather than south-north only, as predicted in current models of the neolithization of coastal Portugal. Seven ceramics and seven sediments were selected for elemental analysis. The results supported the patterns in the petrographic analysis. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocytes eliminate tumor cells expressing antigenic peptides in the context of MHC-I molecules. Peptides are generated during protein degradation by the proteasome and resulting products, surviving cytosolic amino-peptidases activity, may be presented by MHC-I molecules. The MHC-I processing pathway is altered in a large number of malignancies and modulation of antigen generation is one strategy employed by cells to evade immune control. In this study we analyzed the generation and presentation of a survivin-derived CTL epitope in HLA-A2-positive colon-carcinoma cells. Although all cell lines expressed the anti-apoptotic protein survivin, some tumors were poorly recognized by ELTLGEFLKL (ELT)-specific CTL cultures. The expression of MHC-I or TAP molecules was similar in all cell lines suggesting that tumors not recognized by CTLs may present defects in the generation of the ELT-epitope which could be due either to lack of generation or to subsequent degradation of the epitope. The cells were analyzed for the expression and the activity of extra-proteasomal peptidases. A significant overexpression and higher activity of TPPII was observed in colon-carcinoma cells which are not killed by ELT-specific CTLs, suggesting a possible role of TPPII in the degradation of the ELT-epitope. To confirm the role of TPPII in the degradation of the ELT-peptide, we showed that treatment of colon-carcinoma cells with a TPPII inhibitor resulted in a dose-dependent increased sensitivity to ELT-specific CTLs. These results suggest that TPPII is involved in degradation of the ELT-peptide, and its overexpression may contribute to the immune escape of colon-carcinoma cells. [ABSTRACT FROM AUTHOR]

CD8+ cytotoxic T lymphocytes (CTL) are important for the immunological control of infections and tumours. Engagement of the T-cell receptor (TCR) with major histocompatibility complex (MHC) class I/peptide complexes on antigen-presenting cells (APC) is the key interaction, which initiates the process of T-cell activation. Depending on the affinity of this interaction, different arrays of signalling pathways and functional outcomes can be activated in the specific T cells. Molecular alterations in the peptide bound to the MHC class I can lead to a lower affinity of the MHC:TCR interaction resulting in incomplete or qualitatively different T-cell responses. Altered peptide ligands (APL) exhibiting such activity are referred to as partial agonists and often occur naturally through genetic instability, which affects T-cell epitopes derived from rapidly mutating viruses or tumour-associated cellular antigens. Partial agonists are usually viewed as peptide variants, which escape efficient CTL recognition. Our recent data suggest that APL can not only trigger incomplete activation but also induce and modulate intrinsic T-cell programmes leading to the shut-off of specific CTL responses. This APL-induced suppression appears to be more prominent in the absence of immunological help, suggesting that under conditions of immune deregulation APL may actively inhibit CTL responses against infectious agents or tumours. In this review, we discuss experimental data supporting this model and possible role of APL-induced immunosuppression in different pathological conditions. [ABSTRACT FROM AUTHOR]

Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days. [ABSTRACT FROM AUTHOR]

Modulation of cytotoxic responses by viral immunoevasins plays an important role in the establishment of latent and persistent viral infections. Together with MHC class-I-restricted CD8T-lymphocytes, non-MHC-restricted natural killer (NK) and lymphokine-activated killer (LAK) cells participate in this anti-viral control. The Us3 protein kinase of herpes simplex virus-1 (HSV-1) inhibits CD8T-cell cytotoxicity, which correlates with the inhibition of granzyme-B (GrB)-induced activation of pro-apoptotic Bid. We have investigated the effect of Us3 on NK and LAK cytotoxicity, because these effectors are believed to share common mechanisms for inducing cell death. We show that, in contrast to their lower sensitivity to CD8T-cell lysis, HSV-1-infected cells are lysed by NK cells or LAK cells as efficiently as the uninfected controls. Both CD8T and NK/LAK effectors were dependent on the activity of GrB and were efficiently blocked by means of treatment with a GrB inhibitor. However, unlike CD8T cells, LAK cells and NK cells failed to induce Bid cleavage, suggesting that various GrB downstream targets be involved in the induction of cell lysis. This finding explains their various sensitivities to viral modulation, which is likely to be important for the respective role of MHC-restricted and non-restricted effectors in the control of HSV-1 infection. [ABSTRACT FROM AUTHOR]

Abstract Accumulating evidence strongly supports the role of lipid rafts in the regulation of T-lymphocyte activation, but the organization and molecular composition of these cholesterol- and sphingolipid-rich membrane microdomains in different subsets of T cells remain poorly investigated. Here, we show that pharmacological disruption of lipid rafts in human CD8+ cytotoxic T-lymphocyte (CTL) clones disturbs the integrity of CD3 complex and CD8 heterodimer, without affecting the reactivity with T-cell receptor (TCR)-specific antibodies. This demonstrates that interaction with completely assembled CD3 complex is not required for the stable expression of TCR at the cell surface. The effect of raft disruption on CD3 and CD8 expression correlates with failure to bind specific tetrameric complexes by a proportion of surface TCR molecules. However, the interaction of specific tetramer with the rest of surface TCR pools appears to be unaffected, demonstrating that TCR-signalling complexes may differ in their requirement for cholesterol to stably maintain their composition and to rearrange for efficient tetramer binding. Together with previously published data, our results support the existence of molecular and/or structural heterogeneity of lipid rafts that may play an important role in controlling distinct functional properties of T-cell subsets. [ABSTRACT FROM AUTHOR]

Plasma cell mucositis (PCM) is a rare benign disease affecting adults characterized by an erythematous mucosa, an epithelial hyperplasia, and a dense submucosal infiltration of mainly mature plasma cells. PCM has been treated with topical, intralesional, and systemic corticosteroids, antibiotics, and topical cyclosporin with unreliable results and questionable benefits. Here, we present a case of PCM, refractory to previous treatments, treated with i-PRF (injectable platelet-rich fibrin) injections. The infiltrations were performed once a week for 2 months. There were no adverse reactions to the treatment. The pain gradually reduced until the score of zero at the fourth infiltration, and the patient remained free of pain during the whole study period. Clinically, we did not obtain a complete healing of the lesion, but a reduced perilesional inflammatory infiltrate was observed at a distance. Therefore, we can conclude that i-PRF has been effective in the management of pain in PMC but does not result in complete healing of the disease., (© 2019 Wiley Periodicals, Inc.)