CD4 +CD25 + regulatory T cells decreased the antitumor activity of cytokine-induced killer (CIK) cells of lung cancer patients.
: CD(4) (+)CD(25) (+) regulatory T cells (Tregs) have been shown to inhibit cytotoxic lymphocytes-mediated immune responses. Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches. Therefore, the purpose of this report was to determine the effect of Tregs on CIK cell growth and CIK-induced cytotoxicity for inhibition of tumor growth in vivo as well as in vitro. After depletion of CD(4) (+)CD(25) (+) cells before culture, the proliferation and cytotoxicity of CIK cells, which indicated in bromodeoxyuridine (BrdU) and lactic dehydrogenase (LDH) assays, were significantly increased. Depletion of CD(4) (+)CD(25) (+) cells preculture also enhanced the suppression effect on the lung cancer cells inoculated in experimental animals. Blockage of glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor beta1 (TGF-beta1) by antibodies partially abrogated the suppressive effect of CD(4) (+)CD(25) (+) cells on CIK. These results indicated that Tregs could inhibit the antitumor activity of CIK cells. The molecules TGF-beta and GITR may contribute to the suppressive function of CD(4) (+)CD(25) (+) cells.
Li
Hui
H
Department of Immunology, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 30060, China, rwziyi@yahoo.com.
Yu
Jin-Pu
JP
Cao
Shui
S
Wei
Feng
F
Zhang
Peng
P
An
Xiu-Mei
XM
Huang
Zong-Tang
ZT
Ren
Xiu-Bao
XB
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit