Phenotypic and functional evaluation of CD3(+)CD4(-)CD8(-) T cells in human CD8 immunodeficiency
Por:
Bernardo, I, Mancebo, E, Aguilo, 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
Publicada:
1 ago 2011
Resumen:
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 CD8 alpha.
Results
CD8 alpha 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 naive T cells were under-represented. A low concentration of T-cell receptor excision circles together with a skewed T-cell receptor-V beta 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.
Filiaciones:
Bernardo, I:
Hosp Univ 12 Octubre, Serv Inmunol, Madrid 28041, Spain
Mancebo, E:
Hosp Univ 12 Octubre, Serv Inmunol, Madrid 28041, Spain
Aguilo, I:
Univ Zaragoza, Dept Bioquim Biol Mol & Celular, Zaragoza, Spain
Anel, A:
Univ Zaragoza, Dept Bioquim Biol Mol & Celular, Zaragoza, Spain
Allende, LM:
Hosp Univ 12 Octubre, Serv Inmunol, Madrid 28041, Spain
Guerra-Vales, JM:
Hosp Univ 12 Octubre, Med Interna Serv, Madrid 28041, Spain
Ruiz-Contreras, J:
Hosp Univ 12 Octubre, Serv Pediatria, Secc Inmunodeficiencias, Madrid 28041, Spain
Serrano, A:
Hosp Univ 12 Octubre, Serv Inmunol, Madrid 28041, Spain
Talayero, P:
Hosp Univ 12 Octubre, Serv Inmunol, Madrid 28041, Spain
de la Calle, O:
Hosp Santa Creu & Sant Pau, Serv Inmunol, Barcelona, Spain
Gonzalez-Santesteban, C:
Hosp Santa Creu & Sant Pau, Serv Inmunol, Barcelona, Spain
Paz-Artal, E:
Hosp Univ 12 Octubre, Serv Inmunol, Madrid 28041, Spain
Gold, Green Published
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