title: Profile of regulatory T cells and interferon γ secretion in the tumor-draining lymph node from mouse Hepa1-6 cells.
abstract: BACKGROUND
  The tumor-draining lymph node (TDLN) is the critical and initial site of the immune decision made between activation and tolerance to tumor antigens. Tumor-reactive lymphadenopathy in TDLN has been observed for decades, but the profiles of immune regulation in these nodes remain unclear.
  
  
  METHODS
  Both regulatory T cells (Tregs) and effector T cells were examined using 6 × 10(5) Hepa1-6 hepatocellular carcinoma cells implanted in footpads of syngeneic C57BL/6J mice, which formed TDLN. FOXP3(+) Tregs and CD8(+) T cells in TDLN were detected by immunohistochemical staining. The frequency of CD4(+)FOXP3(+) T cells and FOXP3 mRNA expression were determined by flow cytometry and real-time quantitative polymerase chain reaction. The interferon γ secretion ability of CD8(+) T cells in TDLN was measured by enzyme-linked immunospot technique.
  
  
  RESULTS
  There was significant expansion of Tregs and CD8(+) T cells in the tumor-draining popliteal lymph node compared with nondraining popliteal lymph node and spleen in the same mouse. Tregs were diffusely distributed in the CD8(+) T cell compartment. The CD8(+) T cells primed in TDLN showed a strong ability of interferon γ secretion via in vitro stimulation.
  
  
  CONCLUSIONS
  These findings support the notion that Tregs suppress CD8(+) T cells by secreting cytokines such as transforming growth factor β and interleukin 10, but do not make CD8(+) T cells lose function in the TDLN. Deletion of Tregs at the secondary lymphoid organs could be crucial for the establishment of a tumor-specific immunotherapy.
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Kuang
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Hua
authors.forename: Qiang
authors.initials: Q
authors.lastname: He
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Bao-Gang
authors.initials: BG
authors.lastname: Peng
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CD8(+) T cells; Hepa1–6; Immune tolerance; Regulatory T cells; Tumor-draining lymph node