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SIMPOSIUM The Transplantation Society – THYMUS-DERIVED TREG INFUSION TO PREVENT GRAFT REJECTION IN HEART-TRANSPLANTED CHILDREN: INITIAL EXPLORATION OF A NEW THERAPEUTIC ARSENAL TO BOOST IMMUNE TOLERANCE.

Rafael Correa-Rocha; Esther Bernaldo de Quirós; VerónicaA. Pérez; Maribel Clemente; Juan Miguel Gil-Jaurena; María Teresa González; Marjorie Pion; Giovanna Lombardi; LoriJ. West; Megan Levings. 2017 – Transplantation Science Symposium Introduction: Immune graft rejection is the main obstacle to successful transplants. Immunosuppressive drugs fail to prevent chronic rejection and also impair the immune system, resulting in reduced lifetime survival rates. Transfer of regulatory T cells (Treg) has acquired growing interest in attempts to achieve indefinite graft survival [1]. The limited Treg numbers that can be purified from peripheral blood, along with low survival and limited suppressive capacity of expanded Treg obtained from adults,… Leer más »SIMPOSIUM The Transplantation Society – THYMUS-DERIVED TREG INFUSION TO PREVENT GRAFT REJECTION IN HEART-TRANSPLANTED CHILDREN: INITIAL EXPLORATION OF A NEW THERAPEUTIC ARSENAL TO BOOST IMMUNE TOLERANCE.

The establishment of cow’s milk protein allergy in infants is related with a deficit of regulatory T cells (Treg) and vitamin D.

Laura Perezabad, Jacobo López-Abente, Elena Alonso-Lebrero, Elena Seoane, Marjorie Pion, Rafael Correa-Rocha. Pediatr Res. 2017 May;81(5):722-730. Epub 2017 Jan 18. DOI: 10.1038/pr.2017.12 Abstract Background:  Cow’s milk protein allergy (CMPA) is the most common food allergy in infants. However, little is known about which specific immune mechanisms are related with the CMPA onset. The objective was to investigate which immune alterations constitute differential factors between allergy and tolerance, and hence could be implicated in the CMPA establishment in infants. Methods:  An extensive analysis of immune subsets, including Treg and cytokine-secreting cells was performed in blood samples from 28 infants younger than 9 mo obtained 1-4 d after the first… Leer más »The establishment of cow’s milk protein allergy in infants is related with a deficit of regulatory T cells (Treg) and vitamin D.

Functional Mechanisms of Treg in the Context of HIV Infection and the Janus Face of Immune Suppression.

Jacobo López-Abente, Rafael Correa-Rocha, Marjorie Pion. Front Immunol 2016 May 19;7:192. eCollection 2016. DOI: 10.3389/fimmu.2016.00192 Abstract Regulatory T cells (Tregs) play an important role in infections, by modulating host immune responses and avoiding the overreactive immunity that in the case of human immunodeficiency virus (HIV) infection leads to a marked erosion and deregulation of the entire immune system. Therefore, the suppressive function of Treg in HIV-infected patients is critical because of their implication on preventing the immune hyperactivation, even though it could also have a detrimental effect by suppressing HIV-specific immune responses. In recent years, several studies have shown that HIV-1 can directly… Leer más »Functional Mechanisms of Treg in the Context of HIV Infection and the Janus Face of Immune Suppression.

Nanotechnology as a New Therapeutic Approach to Prevent the HIV-Infection of Treg Cells.

Didiana Jaramillo-Ruiz, Francisco Javier De La Mata, Rafael Gómez, Rafael Correa-Rocha, M Ángeles Muñoz-Fernández. PLoS One. 2016 Jan 19;11(1):e0145760. eCollection 2016. DOI: 10.1371/journal.pone.0145760 Abstract Background: HIV-1 has proved to infect regulatory T cells (Treg) modifying their phenotype and impairing their suppressive capacity. As Treg cells are a crucial component in the preservation of the immune homeostasis, we researched that the antiviral capacity of carboxilan dendrimers prevents the HIV-1 infection of Treg and their effects. The phenotype and suppressive capacity of Treg treated or non-treated with carbosilane dendrimers were studied by flow cytometry. Treated and non-treated Treg from healthy donors were infected with HIV-1NL4.3. The infection of… Leer más »Nanotechnology as a New Therapeutic Approach to Prevent the HIV-Infection of Treg Cells.

HIV-1 induces B-cell activation and class switch recombination via spleen tyrosine kinase and c-Jun N-terminal kinase pathways.

Ana Judith Perisé-Barrios, Rafael Correa-Rocha, Susana Alvarez, Maria Angeles Muñoz-Fernandez, Marjorie Pion. AIDS 2014 Oct 23;28(16):2365-74. Abstract Objective:  Patients infected by the HIV type 1 (HIV-1) frequently show a general deregulation of immune system. A direct influence of HIV-1 particles on B-cell activation, proliferation and B-cell phenotype alterations has been recently described. Moreover, expression of activation-induced cytidinedeaminase (AID) mRNA, which is responsible for class switch recombination (CSR) and somatic hypermutation (SHM), was reported to be overexpressed in B cells exposed to HIV-1. Design:  Study of primary human B cells in an in-vitro model. Methods:  In the current study, we evaluated which signalling pathways are… Leer más »HIV-1 induces B-cell activation and class switch recombination via spleen tyrosine kinase and c-Jun N-terminal kinase pathways.

HIV-1 induces B-cell activation and class switch recombination via spleen tyrosine kinase and c-Jun N-terminal kinase pathways.

Gema Méndez-Lagares, Didiana Jaramillo-Ruiz, Marjorie Pion, Manuel Leal, M A Muñoz-Fernández, Yolanda M Pacheco, Rafael Correa-Rocha. J Acquir Immune Defic Syndr . 2014 Mar 1;65(3):278-82. DOI: 10.1097/QAI.0000000000000092 Abstract Indexation of regulatory T cells (Treg) to the number of activated T cells constitutes a homeostatic mechanism ensuring that T-cell expansion remains under control. However, immune hyperactivation observed in HIV-infected patients suggests a possible dysfunction of this mechanism. Here we show that the Treg/IL-2-producing cells’ balance is deeply disturbed in viremic HIV-infected patients. We found a lower expression of IL-2 receptor alpha on Treg from viremic patients. We confirmed in vitro that HIV infection of Treg downregulates IL-2 receptor alpha… Leer más »HIV-1 induces B-cell activation and class switch recombination via spleen tyrosine kinase and c-Jun N-terminal kinase pathways.

Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 22q11.2 deletion syndrome.

Sara Ferrando-Martínez, Raquel Lorente, Dolores Gurbindo, Ma Isabel De José, Manuel Leal, Ma Angeles Muñoz-Fernández, Rafael Correa-Rocha. J Pediatr. 2014 Apr;164(4).Epub 2014 Jan 23. Abstract Objective: To perform an extensive analysis of the immune status of asymptomatic children with the 22q11.2 deletion syndrome, with special emphasis on the regulatory T cells (Treg) population. Study design: Analysis of thymic function, frequency and absolute counts of immune subsets, and phenotype of Treg were performed in 10 asymptomatic children bearing the 22q11.2 deletion and compared with 12 age-matched, healthy children. Results: Children with 22q11.2 deletion syndrome showed a curtailed thymic output, lower T-cell levels, and a homeostatic deregulation in the CD4 T-cell compartment,… Leer más »Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 22q11.2 deletion syndrome.

Induction of Treg cells after oral immunotherapy in hen’s egg-allergic children.

Victoria Fuentes-Aparicio, Elena Alonso-Lebrero, Lidia Zapatero, Sonsoles Infante, Raquel Lorente, M Ángeles Muñoz-Fernández, Rafael Correa-Rocha. Pediatr Allergy Immunol  2014 Feb;25(1):103-6. Epub 2013 Oct 7. DOI: 10.1111/pai.12137 Induction of Treg cells after oral immunotherapy in hen’s egg‐allergic children – Fuentes‐Aparicio – 2014 – Pediatric Allergy and Immunology – Wiley Online Library

HIV infection of human regulatory T cells downregulates Foxp3 expression by increasing DNMT3b levels and DNA methylation in the FOXP3 gene.

Marjorie Pion, Didiana Jaramillo-Ruiz, Alberto Martínez, M Angeles Muñoz-Fernández, Rafael Correa-Rocha. AIDS 2013 Aug 24;27(13):2019-29.  DOI: 10.1097/QAD.0b013e32836253fd Abstract Objective: Regulatory T cells (Tregs) play an important role in infections modulating host immune responses and avoiding overreactive immunity. The mechanisms underlying their action in HIV-infected patients have not been well established. HIV can infect Treg, but little is known about the effects of the infection on Treg phenotype and function. The objective of this study was to investigate whether in-vitro HIV infection modifies the phenotype and suppressive capacity of Treg cells. Design: Because Treg cells are a subset of CD4 T cells, HIV infection could produce alterations in… Leer más »HIV infection of human regulatory T cells downregulates Foxp3 expression by increasing DNMT3b levels and DNA methylation in the FOXP3 gene.

Oral immunotherapy in hen’s egg-allergic children increases a hypo-proliferative subset of CD4+ T cells that could constitute a marker of tolerance achievement.

Victoria Fuentes-Aparicio, Elena Alonso-Lebrero, Lidia Zapatero, Sonsoles Infante, Raquel Lorente, Ma Ángeles Muñoz-Fernández, Rafael Correa-Rocha. Pediatr Allergy Immunol . 2012 Nov;23(7):648-53. Epub 2012 Jul 26. DOI: 10.1111/j.1399-3038.2012.01333.x Abstract Background: Food allergy affects a significant number of children and its prevalence, and persistence is undergoing an important increase in the last years. Specific oral tolerance induction (SOTI) is a promising therapy for food allergy. However, little is known about the immune mechanisms implicated in the desensitization to allergens. Our purpose was to study which immune parameters are modified during the process of tolerance achievement with the goal of identifying markers of tolerance induction. Methods: We performed… Leer más »Oral immunotherapy in hen’s egg-allergic children increases a hypo-proliferative subset of CD4+ T cells that could constitute a marker of tolerance achievement.