6 results on '"Recio MJ"'
Search Results
2. Natural killer cell hyporesponsiveness and impaired development in a CD247-deficient patient.
- Author
-
Valés-Gómez M, Esteso G, Aydogmus C, Blázquez-Moreno A, Marín AV, Briones AC, Garcillán B, García-Cuesta EM, López Cobo S, Haskologlu S, Moraru M, Cipe F, Dobbs K, Dogu F, Parolini S, Notarangelo LD, Vilches C, Recio MJ, Regueiro JR, Ikinciogullari A, and Reyburn HT
- Subjects
- Gene Expression, Genotype, Humans, CD3 Complex genetics, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Sequence Deletion
- Published
- 2016
- Full Text
- View/download PDF
3. Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression.
- Author
-
Muñoz-Ruiz M, Pérez-Flores V, Garcillán B, Guardo AC, Mazariegos MS, Takada H, Allende LM, Kilic SS, Sanal O, Roifman CM, López-Granados E, Recio MJ, Martínez-Naves E, Fernández-Malavé E, and Regueiro JR
- Subjects
- Cell Membrane metabolism, Humans, Models, Immunological, T-Lymphocytes immunology, CD3 Complex immunology, Haploinsufficiency immunology, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, Antigen, T-Cell, gamma-delta immunology
- Abstract
Background: The T cell antigen receptors (TCR) of αβ and γδ T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, αβ or γδ TCR chains incorporate a CD3δε dimer, then a CD3γε dimer and finally a ζζ homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3γ and CD3δ proteins would thus be expected to have a similar impact in the assembly and surface expression of both TCR isotypes. To test this hypothesis, we compared the surface TCR expression of primary αβ and γδ T cells from healthy donors carrying a single null or leaky mutation in CD3G (γ+/-) or CD3D (δ+/-, δ+/leaky) with that of normal controls., Results: Although the partial reduction in the intracellular availability of CD3γ or CD3δ proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3ε antibodies was significantly more decreased in γδ than in αβ T lymphocytes in CD3γ+/- individuals, whereas CD3δ+/- and CD3δ+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface γδ TCR expression was more dependent on available CD3γ than surface αβ TCR expression., Conclusions: The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3γε and CD3δε dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3γ, but not of the homologous CD3δ chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.
- Published
- 2013
- Full Text
- View/download PDF
4. A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ-Tγδ+B+NK+ human SCID.
- Author
-
Gil J, Busto EM, Garcillán B, Chean C, García-Rodríguez MC, Díaz-Alderete A, Navarro J, Reiné J, Mencía A, Gurbindo D, Beléndez C, Gordillo I, Duchniewicz M, Höhne K, García-Sánchez F, Fernández-Cruz E, López-Granados E, Schamel WW, Moreno-Pelayo MA, Recio MJ, and Regueiro JR
- Subjects
- Animals, B-Lymphocytes immunology, Base Sequence, DNA Mutational Analysis, Female, Humans, Infant, Killer Cells, Natural immunology, Male, Mice, Pedigree, RNA Splice Sites genetics, Receptors, Antigen, T-Cell, alpha-beta metabolism, Receptors, Antigen, T-Cell, gamma-delta metabolism, Severe Combined Immunodeficiency etiology, CD3 Complex genetics, Mutation, Severe Combined Immunodeficiency genetics, Severe Combined Immunodeficiency immunology, T-Lymphocyte Subsets immunology
- Abstract
T 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.
- Published
- 2011
- Full Text
- View/download PDF
5. CD3γ-independent pathways in TCR-mediated signaling in mature T and iNKT lymphocytes.
- Author
-
Reiné J, Busto EM, Muñoz-Ruiz M, Rossi NE, Rodríguez-Fernández JL, Martínez-Naves E, Regueiro JR, and Recio MJ
- Subjects
- Adult, Animals, CD3 Complex genetics, CD3 Complex metabolism, Cell Line, Transformed, Cell Proliferation drug effects, Cells, Cultured, Female, Flow Cytometry, Galactosylceramides immunology, Galactosylceramides pharmacology, Humans, Immunoblotting, Male, Mice, Mice, Knockout, Mutation, Natural Killer T-Cells metabolism, Phosphorylation, Receptor-CD3 Complex, Antigen, T-Cell immunology, Receptor-CD3 Complex, Antigen, T-Cell metabolism, Receptors, Antigen, T-Cell metabolism, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, Antigen, T-Cell, alpha-beta metabolism, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Young Adult, CD3 Complex immunology, Natural Killer T-Cells immunology, Receptors, Antigen, T-Cell immunology, Signal Transduction immunology, T-Lymphocytes immunology
- Abstract
Antigen recognition by T-lymphocytes through the T-cell antigen receptor, TCR-CD3, is a central event in the initiation of an immune response. CD3 proteins may have redundant as well as specific contributions to the intracellular propagation of TCR-mediated signals. However, to date, the relative role that each CD3 chain plays in signaling is controversial. In order to examine the roles of CD3γ chain in TCR signaling, we analyzed proximal and distal signaling events in human CD3γ(-/-) primary and Herpesvirus saimiri (HVS)-transformed T cells. Following TCR-CD3 engagement, certain early TCR signaling pathways (ZAP-70, ERK, p38 and mTORC2 phosphorylation, and actin polymerization) were comparable with control HVS-transformed T cells. However, other signaling pathways were affected, such TCRζ phosphorylation, indicating that the CD3γ chain contributes to improve TCR signaling efficiency and survival. On the other hand, CD3γ(-/-) primary invariant NKT cells (iNKT cells) showed a normal expansion in response to alpha-galactosylceramide (α-GalCer) and TCRVβ11(bright) iNKT cells were preferentially selected in this in vitro culture system, perhaps as a consequence of selective events in the thymus. Our results collectively indicate that a TCR lacking CD3γ can propagate a number of signals through the remaining invariant chains, likely the homologous CD3δ chain, which replaces it at the mutant TCR., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
6. Differential biological role of CD3 chains revealed by human immunodeficiencies.
- Author
-
Recio MJ, Moreno-Pelayo MA, Kiliç SS, Guardo AC, Sanal O, Allende LM, Pérez-Flores V, Mencía A, Modamio-Høybjør S, Seoane E, and Regueiro JR
- Subjects
- Adult, Animals, CD3 Complex genetics, Child, Female, Humans, Infant, Leukocyte Common Antigens genetics, Leukocyte Common Antigens immunology, Lymphopenia genetics, Male, Mice, Mutation, Pedigree, Receptors, Antigen, T-Cell, alpha-beta genetics, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, Antigen, T-Cell, gamma-delta genetics, Receptors, Antigen, T-Cell, gamma-delta immunology, Severe Combined Immunodeficiency genetics, Spain, T-Lymphocytes immunology, Thymus Gland immunology, Turkey, CD3 Complex immunology, Lymphopenia immunology, Severe Combined Immunodeficiency immunology
- Abstract
The biological role in vivo of the homologous CD3gamma and delta invariant chains within the human TCR/CD3 complex is a matter of debate, as murine models do not recapitulate human immunodeficiencies. We have characterized, in a Turkish family, two new patients with complete CD3gamma deficiency and SCID symptoms and compared them with three CD3gamma-deficient individuals belonging to two families from Turkey and Spain. All tested patients shared similar immunological features such as a partial TCR/CD3 expression defect, mild alphabeta and gammadelta T lymphocytopenia, poor in vitro proliferative responses to Ags and mitogens at diagnosis, and very low TCR rearrangement excision circles and CD45RA(+) alphabeta T cells. However, intrafamilial and interfamilial clinical variability was observed in patients carrying the same CD3G mutations. Two reached the second or third decade in healthy conditions, whereas the other three showed lethal SCID features with enteropathy early in life. In contrast, all reported human complete CD3delta (or CD3epsilon) deficiencies are in infants with life-threatening SCID and very severe alphabeta and gammadelta T lymphocytopenia. Thus, the peripheral T lymphocyte pool was comparatively well preserved in human CD3gamma deficiencies despite poor thymus output or clinical outcome. We propose a CD3delta >> CD3gamma hierarchy for the relative impact of their absence on the signaling for T cell production in humans.
- Published
- 2007
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.