Person: Regueiro González-Barros, José Ramón
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First Name
José Ramón
Last Name
Regueiro González-Barros
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Inmunología
Identifiers
4 results
Search Results
Now showing 1 - 4 of 4
Item Natural killer cell hyporesponsiveness and impaired development in a CD247-deficient patient(Journal of Allergy and Clinical Immunology, 2016) Valés Gómez, Mar; Esteso, Gloria; Aydogmus, Cigdem; Blázquez Moreno, Alfonso; Marín Marín, Ana Victoria; Briones Contreras, Alejandro; Garcillán Goyoaga, Beatriz de; García Cuesta, Eva; López Cobo, Sheila; Haskologlu, Sule; Moraru, Manuela; Cipe, Funda E; Dobbs, Kerry; Dogu, Figen; Parolini, Silvia; Notarangelo, Luigi D.; Vilches, Carlos; Recio Hoyas, María José; Regueiro González-Barros, José Ramón; Ikinciogullari, Aydan; Reyburn, Hugh T. RItem A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ−Tγδ+B+NK+ human SCID(The Journal of Clinical Investigation, 2011) Gil Calle, Juana Nelly; Busto, Elena M; Garcillán Goyoaga, Beatriz de; Chean, Carmen; García Rodríguez, María Cruz; Díaz Alderete, Andrea; Navarro, Joaquín; Reiné Gutiérrez, Jesús; Mencía, Ángeles; Gurbindo, Dolores; Beléndez, Cristina; Gordillo, Isabel; Duchniewicz, Marlena; Höhne, Kerstin; García Sánchez, Félix; Fernández Cruz, Eduardo; López Granados, Eduardo; Schamel, Wolfgang W.A.; Moreno Pelayo, Miguel A; Recio Hoyas, María José; Regueiro González-Barros, José RamónT cells recognize antigens via their cell surface TCR and are classified as either αβ or γδ depending on the variable chains in their TCR, α and β or γ and δ, respectively. Both αβ and γδ TCRs also contain several invariant chains, including CD3δ, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3δ-deficient patients described to date showed a complete block in T cell development. However, CD3δ-KO mice have an αβ T cell–specific defect. Here, we report 2 unrelated cases of SCID with a selective block in αβ but not in γδ T cell development, associated with a new splicing mutation in the CD3D gene. The patients’ T cells showed reduced CD3D transcripts, CD3δ proteins, surface TCR, and early TCR signaling. Their lymph nodes showed severe T cell depletion, recent thymus emigrants in peripheral blood were strongly decreased, and the scant αβ T cells were oligoclonal. T cell–dependent B cell functions were also impaired, despite the presence of normal B cell numbers. Strikingly, despite the specific loss of αβ T cells, surface TCR expression was more reduced in γδ than in αβ T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3δ requirements for αβ versus γδ T cell development and TCR expression in humans and highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected.Item The CD3 Conformational Change in the gd T Cell Receptor Is Not Triggered by Antigens but Can Be Enforced to Enhance Tumor Killing(Cell Reports, 2014) Dopfer, Elaine P; Hartl, Frederike A; Oberg, Hans-Heinrich; Siegers, Grabrielle M; Yousefi, S. Sascha; Kock, Sylvia; Fiala, Gina J; Garcillán Goyoaga, Beatriz de; Sandstrom, Andrew; Alarcón, Balbino; Regueiro González-Barros, José Ramón; Kabelitz, Dieter; Adams, Erin J; Minguet, Susana; Wesch, Daniela; Fisch, Paul; Schamel, Wolfgang W.A.Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the ab TCR antigen induces a conformational change at the CD3 subunits (CD3 CC) that is absolutely required for abTCR activation. Here, we demonstrate that the CD3 CC is not induced by antigen stimulation of the mouse G8 or the human Vg9Vd2 gdTCR. We find that there is a fundamental difference between the activation mechanisms of the abTCR and gdTCR that map to the constant regions of the TCRab/gd heterodimers. Enforced induction of CD3 CC with a less commonly used monoclonal anti-CD3 promoted proximal gdTCR signaling but inhibited cytokine secretion. Utilizing this knowledge, we could dramatically improve in vitro tumor cell lysis by activated human gd T cells. Thus, manipulation of the CD3 CC might be exploited to improve clinical gd T cellbased immunotherapies.Item gd T lymphocytes in the diagnosis of human T cell receptor immunodeficiencies(Frontiers in immunology, 2015) Garcillán Goyoaga, Beatriz de; Marín Marín, Ana Victoria; Jiménez Reinoso, Anaïs; Briones Contreras, Alejandro; Muñoz Ruiz, Miguel; García León, María J; Gil Calle, Juana Nelly; Allende Martínez, Luis Miguel; Martínez Naves, Eduardo; Toribio, Maria Luisa; Regueiro González-Barros, José RamónHuman T cell receptor (TCR) immunodeficiencies (TCRID) are rare autosomal recessive disorders caused by mutations affecting TCR, CD3, or CD247 chains, which share developmental, functional, and TCR expression defects (1). Their rapid diagnosis is fundamental for patient survival and early hematopoietic stemcell transplantation.Here,we propose that studying gd T cells, which are often neglected, can be helpful for a timely diagnosis. We thus offer a diagnostic flowchart and some lab tricks based on published cases.