CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion.
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.


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.
Chen
Yi-Qiang
YQ
Institute of Respiratory Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, P. R. China. hzshi@vip.tom.com
Shi
Huan-Zhong
HZ
Qin
Xue-Jun
XJ
Mo
Wu-Ning
WN
Liang
Xiang-Dong
XD
Huang
Ze-Xin
ZX
Yang
Hai-Bo
HB
Wu
Cong
C
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D015704:CD4 Antigens / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2