Bernardo, IvánMancebo Sierra, María EstherAguiló, IgnacioAnel, AlbertoAllende Martínez, Luis MiguelGuerra Vales, Juan ManuelRuiz Contreras, JesúsSerrano, AntonioTalayero, Palomade la Calle, ÓscarGonzalez-Santesteban, CeciliaPaz Artal, Estela Natividad2024-02-052024-02-052011Bernardo I, Mancebo E, Aguiló I, Anel A, Allende LM, Guerra-Vales JM, Ruiz-Contreras J, Serrano A, Talayero P, de la Calle O, Gonzalez-Santesteban C, Paz-Artal E. Phenotypic and functional evaluation of CD3+CD4-CD8- T cells in human CD8 immunodeficiency. Haematologica. 2011 Aug;96(8):1195-203. doi: 10.3324/haematol.2011.041301. Epub 2011 May 5. PMID: 21546492; PMCID: PMC3148914.0390-607810.3324/haematol.2011.041301https://hdl.handle.net/20.500.14352/98888Derechos reservados de Haematologica. Ferrari Storti Foundation http://www.haematologica.org/Background: Human CD8 immunodeficiency is characterized by undetectable CD8(+) lymphocytes and an increased population of CD4(-)CD8(-) (double negative) T lymphocytes. Design and methods: We hypothesized that the double negative subset corresponds to the cellular population that should express CD8 and is committed to the cytotoxic T lymphocyte lineage. To assess this, we determined the phenotype and function of peripheral blood mononuclear cells and/or magnetically isolated double negative T lymphocytes from two CD8-deficient patients. To analyze the expression and co-localization with different organelles, 293T cells were transfected with plasmids bearing wild-type or mutated CD8α. Results: CD8α mutated protein was retained in the cytoplasm of transfected cells. The percentages of double negative cells in patients were lower than the percentages of CD8(+) T cells in healthy controls. Double negative cells mostly had an effector or effector memory phenotype whereas naïve T cells were under-represented. A low concentration of T-cell receptor excision circles together with a skewed T-cell receptor-V repertoire were observed in the double negative population. These data suggest that, in the absence of CD8 co-receptor, the thymic positive selection functions suboptimally and a limited number of mature T-cell clones would emerge from the thymus. In vitro, the double negative cells showed a mild defect in cytotoxic function and decreased proliferative capacity. Conclusions: It is possible that the double negative cells are major histocompatibility complex class-I restricted T cells with cytolytic function. These results show for the first time in humans that the presence of the CD8 co-receptor is dispensable for cytotoxic ability, but that it affects the generation of thymic precursors committed to the cytotoxic T lymphocyte lineage and the proliferation of mature cytotoxic T cells.engjournal article1592-8721https://doi.org/10.3324/haematol.2011.04130121546492https://pubmed.ncbi.nlm.nih.gov/21546492/open access616.15:612.017Ciencias BiomédicasInmunología32 Ciencias Médicas