Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation.

Ag-experienced or memory T cells have increased reactivity to recall Ag, and can be distinguished from naive T cells by altered expression of surface markers such as CD44. Memory T cells have a high turnover rate, and CD8(+) memory T cells proliferate upon viral infection, in the presence of IFN-alphabeta and/or IL-15. In this study, we extend these findings by showing that activated NKT cells and superantigen-activated T cells induce extensive bystander proliferation of both CD8(+) and CD4(+) memory T cells. Moreover, proliferation of memory T cells can be induced by an IFN-alphabeta-independent, but IFN-gamma- or IL-12-dependent pathway. In these conditions of bystander activation, proliferating memory (CD44(high)) T cells do not derive from activation of naive (CD44(low)) T cells, but rather from bona fide memory CD44(high) T cells. Together, these data demonstrate that distinct pathways can induce bystander proliferation of memory T cells.

CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.

We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1. In the present study, we have analyzed in detail the relative antigenicity and in vitro immunogenicity of natural and modified NY-ESO-1 peptide sequences. The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients. In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently. In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level. Among natural peptides, NY-ESO-1 157-165 and NY-ESO-1 157-167 exhibited good in vitro immunogenicity, whereas peptide NY-ESO-1 155-163 was poorly immunogenic. The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions. The findings reported here have significant implications for the formulation of NY-ESO-1-based vaccines as well as for the monitoring of either natural or vaccine-induced NY-ESO-1-specific CTL responses in cancer patients.

Estudi i anàlisi de la violència i els joves que es troben en disposició dels serveis judicials

Aquest treball tracta sobre la violència. Específicament sobre el que els joves entre 14 i 23 anys en pensen. Socialment la violència s’associa al fet de ser home. Per tant, podem pensar que per demostrar la seva virilitat molts homes joves la poden utilitzar. Però, què passa en el cas de les joves? Per què la violència continua sent una eina no de supervivència sinó d’estil de vida? Com podem entendre aquestes subtileses que de vegades s’escapen a primer cop d’ull? Aquest estudi és ambiciós, però al mateix temps realista. Busquem conèixer, entendre i contribuir a crear línies d’accions que facilitin l’eradicació de la violència. Sabem que amb un sol estudi i de curta durada és impossible, però el que volem és iniciar aquest procés. Per això, aquest estudi utilitza una metodologia variada (IAT, fotointervenció i entrevistes) que ha permès veure la part qualitativa, de vegades oblidada, però que ens permet veure, pel seu caràcter il•lustrador, allò que la simple utilització quantitativa no reflecteix per si mateixa. La població estudiada són joves a disposició judicial, pares i mares, professionals del Servei de Justícia i joves que no es troben en disposició judicial. Els resultats obtinguts posen sobre la taula la convivència de les idees tradicionals sobre el que és ser home, el que és ser dona i el que s’entén per violència, amb el mite d’igualtat i no masclisme. Invita a aprofundir en les raons per continuar mantenint la violència com a forma no sols de resolució de conflicte, sinó com a estil de vida lligat al fet de ser d’un sexe o de l’altre i de caràcter immodificable. Des de les dades obtingudes i la seva anàlisi proposem, en termes generals, la continuïtat de la recerca, la formació sobre sexualitat, gènere, violència, vincles, poder, etc. I activitats cap a la sensibilització.

Effect of intermittent hypoxic training on HIF gene expression in human skeletal muscle and leukocytes

Intermittent hypoxic exposure with exercise training is based on the assumption that brief exposure to hypoxia is sufficient to induce beneficial muscular adaptations mediated via hypoxia-inducible transcription factors (HIF). We previously demonstrated (Mounier et al. Med Sci Sports Exerc 38:1410-1417, 2006) that leukocytes respond to hypoxia with a marked inter-individual variability in HIF-1alpha mRNA. This study compared the effects of 3 weeks of intermittent hypoxic training on hif gene expression in both skeletal muscle and leukocytes. Male endurance athletes (n = 19) were divided into an Intermittent Hypoxic Exposure group (IHE) and a Normoxic Training group (NT) with each group following a similar 3-week exercise training program. After training, the amount of HIF-1alpha mRNA in muscle decreased only in IHE group (-24.7%, P < 0.05) whereas it remained unchanged in leukocytes in both groups. The levels of vEGF(121) and vEGF(165) mRNA in skeletal muscle increased significantly after training only in the NT group (+82.5%, P < 0.05 for vEGF(121); +41.2%, P < 0.05 for vEGF(165)). In leukocytes, only the IHE group showed a significant change in vEGF(165) (-28.2%, P < 0.05). The significant decrease in HIF-1alpha mRNA in skeletal muscle after hypoxic training suggests that transcriptional and post-transcriptional regulations of the hif-1alpha gene are different in muscle and leukocytes.