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.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytoplasm / metabolism
  • Cytotoxicity, Immunologic
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Humans
  • Immunophenotyping
  • Mutation / genetics
  • Phenotype*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • CD8 Antigens
  • CD8 antigen, alpha chain
  • CD8 receptor
  • Receptors, Antigen, T-Cell