Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice.
CD25+CD4+ regulatory T cells (Treg) play pivotal roles in the host response to tumors. However, their exact location in vivo is largely unknown. The forkhead/winged helix transcription factor, Foxp3, is specifically expressed in naturally occurring Treg (nTreg) and programs their development and function. In this study, we produced a rabbit polyclonal antibody (pAb), which can detect mouse Foxp3 protein in situ. Results using this pAb revealed that Foxp3+CD4+ nTreg cells occur in direct contact with CD11c+ dendritic cells (DCs), and Foxp3-CD4+ and CD8+T lymphocytes in the T cell regions of lymphoid tissues from normal and tumor-bearing mice. The numbers of Foxp3+CD4+ nTreg cells are significantly increased in draining, but not nondraining, lymph nodes (LNs) and spleen (SPL) of tumor-bearing mice. Furthermore, a small number of nTreg could be also found at the tumor site. These observations support the notion that the numbers of Foxp3+CD4+ nTreg are increased by tumors and may contribute to the immunosuppression observed in tumor-bearing hosts at secondary lymphoid organs and also possibly at the tumor site.
Hontsu
Shigeto
S
Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Yoneyama
Hiroyuki
H
Ueha
Satoshi
S
Terashima
Yuya
Y
Kitabatake
Masahiro
M
Nakano
Akiko
A
Ito
Toshihiro
T
Kimura
Hiroshi
H
Matsushima
Kouji
K
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008198:Lymph Nodes / Q000166:cytology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007202:Indicators and Reagents; D015375:Receptors, Interleukin-2