Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

Eur J Haematol. 2005 Dec;75(6):468-76. doi: 10.1111/j.1600-0609.2005.00537.x.


Purpose: Regulatory T cells (T-reg) that control harmful autoimmune T cells in the periphery may also suppress the immune response against cancer. In this study we investigated the possible involvement of CD4(+)CD25(high) T-reg in the immune impairment of patients with acute myeloid leukemia (AML).

Experimental design: The frequencies and phenotypes of CD4(+)CD25(high) T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4(+)CD25(high) T cells, CD4(+)CD25(high), and CD4(+)CD25(-) T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4(+)CD25(high) and CD4(+)CD25(-) T cells were characterized by proliferation assays and cytokine production assays. In addition, the frequency of apoptotic and proliferating cells in CD4(+)CD25(high) T cells were respectively evaluated by 7AAD and ki67 binding cells using flow cytometry.

Results: Compared with healthy controls, AML patients had a higher proportion of CD4(+)CD25(high) T cells in peripheral blood. These cells were CD45-RA(-), CD69(-), CD45-RO(+), CD95(+), and intercellular CTLA-4(+), and secreted low levels of TNF-alpha and IL-10, but no IL-2, IL-4, IL-5, and IFN-gamma. They inhibited the proliferation and cytokine production (IL-2, IFN-gamma) of CD4(+)CD25(-) T cells, but improved IL-10 production under the co-culture of both subsets with stimulation, thus behaving as T-reg. Notably, CD4(+)CD25(high) T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals.

Conclusions: The frequency of CD4(+)CD25(high) T-reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4(+)CD25(high) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / immunology*
  • CD4 Lymphocyte Count / methods
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Proliferation*
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / blood
  • Cytokines / immunology
  • Female
  • Humans
  • Ki-67 Antigen / immunology
  • Leukemia, Myeloid, Acute / blood
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Receptors, Interleukin-2 / blood
  • Receptors, Interleukin-2 / immunology*


  • Cytokines
  • Ki-67 Antigen
  • Receptors, Interleukin-2