Receptores de citocinas proinflamatórias na pré-eclâmpsia

Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-αR1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-αR1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-αR1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- αR1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.

A deimmunised form of the ribotoxin, α-sarcin, lacking CD4+ T cell epitopes and its use as an immunotoxin warhead

Fungal ribotoxins that block protein synthesis can be useful warheads in the context of a targeted immunotoxin. α-Sarcin is a small (17 kDa) fungal ribonuclease produced by Aspergillus giganteus that functions by catalytically cleaving a single phosphodiester bond in the sarcin–ricin loop of the large ribosomal subunit, thus making the ribosome unrecognisable to elongation factors and leading to inhibition of protein synthesis. Peptide mapping using an ex vivo human T cell assay determined that α-sarcin contained two T cell epitopes; one in the N-terminal 20 amino acids and the other in the C-terminal 20 amino acids. Various mutations were tested individually within each epitope and then in combination to isolate deimmunised α-sarcin variants that had the desired properties of silencing T cell epitopes and retention of the ability to inhibit protein synthesis (equivalent to wild-type, WT α-sarcin). A deimmunised variant (D9T/Q142T) demonstrated a complete lack of T cell activation in in vitro whole protein human T cell assays using peripheral blood mononuclear cells from donors with diverse HLA allotypes. Generation of an immunotoxin by fusion of the D9T/Q142T variant to a single-chain Fv targeting Her2 demonstrated potent cell killing equivalent to a fusion protein comprising the WT α-sarcin. These results represent the first fungal ribotoxin to be deimmunised with the potential to construct a new generation of deimmunised immunotoxin therapeutics.

Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T cells : Implications for HIV Microbicides

This work was supported by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement No 305316 as part of the MOTIF (Microbicides Optimisation Through Innovative Formulation for Vaginal and Rectal Delivery) project. We would like to extend our thanks to all the study participants for their invaluable contribution and to Grampian Biorepository staff for help with collection of fresh colorectal resection tissue.

Étude de l'interaction CCL20/CCR6 et de son rôle dans l'homéostasis des lymphocytes T

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Étude du développement des lymphocytes T mémoires

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Rôle des caspases et des granzymes dans la régulation de la réponse immune : implication différentielle dans la prolifération et l'apoptose des lymphocytes T

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Évolution des réponses CD4 et CD8 dirigés contre le VIH au cours de l'infection

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

L'interleukine-21 : un nouveau joueur dans l'homéostasie des lymphocytes T mémoires CD8 ⁺ et dans l'hématopoïèse

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Rôle du CD46 dans le développement et la fonction des lymphocytes T régulateurs naturels

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Capacité de rétention du récepteur CD4 par la protéine Vpu du VIH-1 chez des isolats primaires et implications au niveau de l'infectivité des particules virales

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Développement des lymphocytes T : mécanismes de différenciation extrathymique

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Les lymphocytes T mémoires... une question de survie

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Caractérisation des motifs permettant la mobilisation vers les endosomes et la présentation par les molécules du CMH de classe II chez gp100 : un antigène du mélanome

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Traitement du cancer par transfert adoptif de lymphocytes T dirigés contre un antigène mineur d'histocompatibilité

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A Brief Chronicle of CD4 as a Biomarker for HIV/AIDS: A Tribute to the Memory of John L. Fahey.

Foundational cellular immunology research of the 1960s and 1970s, together with the advent of monoclonal antibodies and flow cytometry, provided the knowledge base and the technological capability that enabled the elucidation of the role of CD4 T cells in HIV infection. Research identifying the sources and magnitude of variation in CD4 measurements, standardized reagents and protocols, and the development of clinical flow cytometers all contributed to the feasibility of widespread CD4 testing. Cohort studies and clinical trials provided the context for establishing the utility of CD4 for prognosis in HIV-infected persons, initial assessment of in vivo antiretroviral drug activity, and as a surrogate marker for clinical outcome in antiretroviral therapeutic trials. Even with sensitive HIV viral load measurement, CD4 cell counting is still utilized in determining antiretroviral therapy eligibility and time to initiate therapy. New point of care technologies are helping both to lower the cost of CD4 testing and enable its use in HIV test and treat programs around the world.