This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-3804v1 69/9/3995    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kryczek, I. Articles by Zou, W. Search for Related Content PubMed PubMed Citation Articles by Kryczek, I. Articles by Zou, W.

FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease

Departments of ¹ Surgery, ² Obstetrics and Gynecology, and ³ Medicine, University of Michigan, Ann Arbor, Michigan; and ⁴ Department of Surgery, Union Hospital, Wuhan, People's Republic of China

Requests for reprints: Weiping Zou, Department of Surgery, University of Michigan School of Medicine, 1150 W. Medical Center Dr., MSRBII, rm. 556, Ann Arbor, MI 48109. Phone: 734-615-5554; Fax: 734-763-0143; E-mail: wzou{at}med.umich.edu.

Key Words: cytokine • regulatory T cell • marker • cancer • colitis

Activated T cells may express FOXP3. It is thought that FOXP3 is not a specific marker to determine regulatory T cells (Treg) in humans. Here, we examined the functional phenotype and cytokine profile of the in vitro induced FOXP3⁺ T cells, primary FOXP3⁺ and FOXP3^- T cells in patients with ulcerative colitis and tumors including colon carcinoma, melanoma, hepatic carcinoma, ovarian carcinoma, pancreatic cancer, and renal cell carcinoma. We observed similar levels of suppressive capacity of primary FOXP3⁺ T cells in blood, tumors, and colitic tissues. Compared with primary FOXP3^- T cells in the same microenvironment, these primary FOXP3⁺ T cells expressed minimal levels of effector cytokines, negligible amount of cytotoxic molecule granzyme B, and levels of suppressive molecules interleukin-10 and PD-1. Although the in vitro activated T cells expressed FOXP3, these induced FOXP3⁺ T cells expressed high levels of multiple effector cytokines and were not functionally suppressive. The data reinforce the fact that FOXP3 remains an accurate marker to define primary Tregs in patients with cancer and autoimmune disease. We suggest that the combination of FOXP3 and cytokine profile is useful for further functionally distinguishing primary Tregs from activated conventional T cells. [Cancer Res 2009;69(9):3995–4000]

This article has been cited by other articles:

				C. Jandus, G. Bioley, D. Dojcinovic, L. Derre, L. Baitsch, S. Wieckowski, N. Rufer, W. W. Kwok, J.-M. Tiercy, I. F. Luescher, et al. Tumor Antigen-Specific FOXP3+ CD4 T Cells Identified in Human Metastatic Melanoma: Peptide Vaccination Results in Selective Expansion of Th1-like Counterparts Cancer Res., October 15, 2009; 69(20): 8085 - 8093. [Abstract] [Full Text] [PDF]

				K. Wu, I. Kryczek, L. Chen, W. Zou, and T. H. Welling Kupffer Cell Suppression of CD8+ T Cells in Human Hepatocellular Carcinoma Is Mediated by B7-H1/Programmed Death-1 Interactions Cancer Res., October 15, 2009; 69(20): 8067 - 8075. [Abstract] [Full Text] [PDF]