Suppressive Properties of Human CD4+CD25+ Regulatory T Cells Are Dependent on CTLA-4 Expression

Eur J Immunol. 2004 Dec;34(12):3485-96. doi: 10.1002/eji.200324632.


It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4(+)CD25(+) T cell compartment. Here, we describe an original method to purify human CD4(+)CD25(+)CD152(+) T lymphocytes as living cells by forcing the exportation of CTLA-4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4(+)CD25(+) T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4(+)CD25(+)CD152(+) T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen-specific T cells than CD4(+)CD25(+)CD152(-) T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in CD4(+)CD25(+)CD152(+) T cell regulatory activity, while suppressive cytokines are not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / metabolism*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen
  • Cytokines / metabolism
  • Humans
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Receptors, Interleukin-2 / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • Ionophores
  • Receptors, Interleukin-2
  • Ionomycin