Distribution of CD4+CD25high regulatory T-cells in tumor-draining lymph nodes in patients with gastric cancer.
BACKGROUND
Regulatory T-cells (T-regs) can inhibit the immune response mediated by T-cells. There is an increasing evidence that there is an increased proportion of T-regs in PBLs and tumor-infiltrating lymphocytes in several different human malignancies, although the mechanism remains unclear. In the present study, we evaluated the prevalence of CD4+CD25high T-regs in tumor-draining lymph nodes in patients with gastric cancers.


METHODS
Regional lymph nodes in the stomach of the patients with gastric cancer (n=44) were classified into N1 regional lymph nodes adjacent to the gastric tumor and N2 regional lymph nodes marginally distant from the tumor. The population of CD4+CD25high T-cells as a percentage of total CD4+ cells was evaluated by flow cytometric analysis with triple-color staining. Cytokine production (IL-10 and IFN-gamma) was evaluated by intracellular cytokine staining and the antiproliferative function of CD4+CD25+ cells positively selected by magnetic beads was measured by evaluating the proliferative activity of CD4+CD25- cells in response to anti-CD3 plus anti-CD28 in the presence of autologous CD4+CD25+ cells.


RESULTS
The percentage of CD4+CD25high T-cells in N1 regional lymph nodes (3.1 +/- 0.3%) was significantly higher than that of control mesenteric lymph nodes (1.2 +/- 0.3%, P <0.01). Furthermore, a more extended area (N2) of regional lymph nodes, as well as adjacent lymph nodes (N1) to the tumors, was involved in an increased prevalence of CD4+CD25high T-cells according to the disease progression. The functional evaluations confirmed that CD4+CD25high T-cells derived from the lymph nodes have an inhibitory activity corresponding to T-regs.


CONCLUSIONS
The populations of CD4+CD25high T-cells in the regional lymph nodes in patients with gastric cancer were significantly higher in comparison to those in control lymph nodes. The increased prevalence of T-regs may be one of the explanations for impaired cell-mediated immunity in cancer-bearing hosts.
Kawaida
Hiromichi
H
First Department of Surgery, University of Yamanashi, 1110 Shimokato, Tamaho, Yamanashi 409-3898, Japan.
Kono
Koji
K
Takahashi
Akihiro
A
Sugai
Hidemitsu
H
Mimura
Kosaku
K
Miyagawa
Naoto
N
Omata
Hideo
H
Ooi
Akishi
A
Fujii
Hideki
H
D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D015375:Receptors, Interleukin-2