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Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression.
J Immunol 2005; 175(8):5058-66JI

Abstract

The peripheral tolerance mechanism prevents effective antitumor immunity, even though tumor cells possess recognizable tumor-associated Ags. Recently, it has been elucidated that regulatory T cells (Treg) play a critical role in maintaining not only self-tolerance, but also tolerance of tumor cells. However, because the Treg that maintain self-tolerance arise naturally in the thymus and are thought to be anergic in peripheral, it is still unclear where and when Treg for tumor cells are generated. In this study we analyze tumor-draining lymph nodes (LNs) and demonstrate that both antitumor effector T cells and Treg capable of abrogating the antitumor reactivity of the effector T cells are primed in the same LNs during tumor progression. The regulatory activity generated in tumor-draining LNs exclusively belonged to the CD4(+) T cell subpopulation that expresses both CD25 and a high level of CD62L. Forkhead/winged helix transcription factor gene expression was detected only in the CD62L(high)CD4(+)CD25(+) T cells. CD62L(high)CD4(+)CD25(+) Treg and CD62L(low)CD4(+)CD25(+) T cells, which possess effector T cell functions, had comparable expression of LFA-1, VLA-4, CTLA-4, lymphocyte activation gene-3, and glucocorticoid-induced TNFR. Thus, only CD62L expression could distinguish regulatory CD4(+)CD25(+) cells from effector CD4(+)CD25(+) cells in draining LNs as a surface marker. The Treg generated in tumor-draining LNs possess the same functional properties as the Treg that arise naturally in the thymus but recognize tumor-associated Ag. CD62L(high)CD4(+)CD25(+) Treg contained a subpopulation that expressed CD86. Blocking experiments revealed that ligation of CTLA-4 on effector T cells by CD86 on Treg plays a pivotal role in regulating CD4(+) effector T cells.

Authors+Show Affiliations

Graduate School of Medical and Dental Sciences, Course for Biological Functions and Medical Control, Department of Homeostatic Regulation and Development, Division of Respiratory Medicine, Niigata University, Niigata, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16210609

Citation

Hiura, Toru, et al. "Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes During Tumor Progression." Journal of Immunology (Baltimore, Md. : 1950), vol. 175, no. 8, 2005, pp. 5058-66.
Hiura T, Kagamu H, Miura S, et al. Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression. J Immunol. 2005;175(8):5058-66.
Hiura, T., Kagamu, H., Miura, S., Ishida, A., Tanaka, H., Tanaka, J., ... Yoshizawa, H. (2005). Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression. Journal of Immunology (Baltimore, Md. : 1950), 175(8), pp. 5058-66.
Hiura T, et al. Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes During Tumor Progression. J Immunol. 2005 Oct 15;175(8):5058-66. PubMed PMID: 16210609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression. AU - Hiura,Toru, AU - Kagamu,Hiroshi, AU - Miura,Satoru, AU - Ishida,Akira, AU - Tanaka,Hiroshi, AU - Tanaka,Junta, AU - Gejyo,Fumitake, AU - Yoshizawa,Hirohisa, PY - 2005/10/8/pubmed PY - 2005/12/15/medline PY - 2005/10/8/entrez SP - 5058 EP - 66 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 175 IS - 8 N2 - The peripheral tolerance mechanism prevents effective antitumor immunity, even though tumor cells possess recognizable tumor-associated Ags. Recently, it has been elucidated that regulatory T cells (Treg) play a critical role in maintaining not only self-tolerance, but also tolerance of tumor cells. However, because the Treg that maintain self-tolerance arise naturally in the thymus and are thought to be anergic in peripheral, it is still unclear where and when Treg for tumor cells are generated. In this study we analyze tumor-draining lymph nodes (LNs) and demonstrate that both antitumor effector T cells and Treg capable of abrogating the antitumor reactivity of the effector T cells are primed in the same LNs during tumor progression. The regulatory activity generated in tumor-draining LNs exclusively belonged to the CD4(+) T cell subpopulation that expresses both CD25 and a high level of CD62L. Forkhead/winged helix transcription factor gene expression was detected only in the CD62L(high)CD4(+)CD25(+) T cells. CD62L(high)CD4(+)CD25(+) Treg and CD62L(low)CD4(+)CD25(+) T cells, which possess effector T cell functions, had comparable expression of LFA-1, VLA-4, CTLA-4, lymphocyte activation gene-3, and glucocorticoid-induced TNFR. Thus, only CD62L expression could distinguish regulatory CD4(+)CD25(+) cells from effector CD4(+)CD25(+) cells in draining LNs as a surface marker. The Treg generated in tumor-draining LNs possess the same functional properties as the Treg that arise naturally in the thymus but recognize tumor-associated Ag. CD62L(high)CD4(+)CD25(+) Treg contained a subpopulation that expressed CD86. Blocking experiments revealed that ligation of CTLA-4 on effector T cells by CD86 on Treg plays a pivotal role in regulating CD4(+) effector T cells. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16210609/Both_regulatory_T_cells_and_antitumor_effector_T_cells_are_primed_in_the_same_draining_lymph_nodes_during_tumor_progression_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16210609 DB - PRIME DP - Unbound Medicine ER -