CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion

Am J Respir Crit Care Med. 2005 Dec 1;172(11):1434-9. doi: 10.1164/rccm.200504-588OC. Epub 2005 Sep 8.


Background: Active suppression by CD4(+)CD25(+) regulatory T lymphocytes plays an important role in the downregulation of T-cell responses to foreign and self-antigens.

Objective: To analyze whether the CD4(+)CD25(+) regulatory T lymphocytes exist and function normally in malignant pleural effusion.

Methods: The percentages of CD4(+)CD25(+) T lymphocytes in pleural effusion and peripheral blood from patients with lung cancer with malignant effusion, pleural lavage and peripheral blood from patients with lung cancer without effusion, and peripheral blood from healthy control subjects were determined by flow cytometry. The expressions of forkhead transcription factor Foxp3 and cytotoxic lymphocyte-associated antigen-4 were also examined. CD4(+)CD25(+) and CD4(+)CD25(-) T cells from pleural effusion and peripheral blood were isolated, and were cultured to observe the effects of CD4(+)CD25(+) cells on proliferation response of CD4(+)CD25(-) T cells in vitro.

Main results: There were increased numbers of CD4(+)CD25(+) T cells in malignant pleural effusion from patients with lung cancer compared with pleural lavage from patients with lung cancer without pleural effusion, and that these cells have constitutive high-level expression of Foxp3 and cytotoxic lymphocyte-associated antigen-4. Furthermore, CD4(+)CD25(+) T cells mediate potent inhibition of proliferation response of CD4(+)CD25(-) T cells, and anticytotoxic lymphocyte-associated antigen-4 monoclonal antibody could reduce the inhibitory activity of CD4(+)CD25(+) T cells.

Conclusions: The increased CD4(+)CD25(+) T cells found in malignant pleural effusion express high levels of Foxp3 transcription factor and potently suppress the proliferation of CD4(+)CD25(-) T cells, and cytotoxic lymphocyte-associated antigen-4 is involved in the suppressive activity of pleural CD4(+)CD25(+) T cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD
  • Antigens, Differentiation / pharmacology
  • CD4 Antigens / drug effects
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology*
  • CTLA-4 Antigen
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunoglobulin Fc Fragments / pharmacology
  • Immunosuppressive Agents / pharmacology
  • Male
  • Middle Aged
  • Pleural Effusion, Malignant / drug therapy
  • Pleural Effusion, Malignant / immunology*
  • Pleural Effusion, Malignant / metabolism
  • RNA, Messenger / genetics
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CD4 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunoglobulin Fc Fragments
  • Immunosuppressive Agents
  • RNA, Messenger
  • Receptors, Interleukin-2