RT Journal Article
T1 Phenotypic and functional evaluation of CD3+CD4-CD8- T cells in human CD8 immunodeficiency
A1 Bernardo, Iván
A1 Mancebo Sierra, María Esther
A1 Aguiló, Ignacio
A1 Anel, Alberto
A1 Allende Martínez, Luis Miguel
A1 Guerra Vales, Juan Manuel
A1 Ruiz Contreras, Jesús
A1 Serrano, Antonio
A1 Talayero, Paloma
A1 de la Calle, Óscar
A1 Gonzalez-Santesteban, Cecilia
A1 Paz Artal, Estela Natividad
AB 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.
PB Ferrata Storti Foundation
SN 0390-6078
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/98888
UL https://hdl.handle.net/20.500.14352/98888
LA eng
NO Bernardo 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.
NO Derechos reservados de Haematologica. Ferrari Storti Foundation http://www.haematologica.org/
NO Ministerio de Educación y Ciencia (España)
NO Ministerio de Sanidad y Consumo (España)
DS Docta Complutense
RD 18 abr 2025