FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease

Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Cancer Research (Impact Factor: 9.28). 05/2009; 69(9):3995-4000. DOI: 10.1158/0008-5472.CAN-08-3804
Source: PubMed

ABSTRACT 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.

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    • "For this study, CD3 + CD4 + CD25 + FOXP3 + was used as the principle definition of Treg cells, and results are expressed as percentage of total CD3 + cells. Foxp3 is considered to be highly specific marker for Treg cells [24] [25]. At the end of one year of follow-up time (April 2010), 82 (76%) of sample donors had returned their epidemiological questionnaires to the DBBR for data processing. "
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    ABSTRACT: Immunosuppressive regulatory T (Treg) cells play an important role in antitumor immunity, self-tolerance, transplantation tolerance, and attenuation of allergic response. Higher proportion of Treg cells has been observed in peripheral blood of cancer cases compared to controls. Little is known about potential epidemiological predictors of Treg cell levels in healthy individuals. We conducted a cross-sectional study including 75 healthy women, between 20 and 80 years of age, who participated in the Data Bank and BioRepository (DBBR) program at Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA. Peripheral blood levels of CD4(+)CD25(+)FOXP3(+) Treg cells were measured using flow cytometric analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test, Kruskal-Wallis test, and linear regression. Age, smoking, medications for treatment of osteoporosis, postmenopausal status, body mass index (BMI), and hormone replacement therapy (HRT) were found to be significant positive predictors of Treg cell levels in peripheral blood (P ≤ 0.05). Higher education, exercise, age at first birth, oral contraceptives, and use of Ibuprofen were found be significant (P < 0.05) negative predictors of Treg levels. Thus, various epidemiological risk factors might explain interindividual variation in immune response to pathological conditions, including cancer.
    Journal of Cancer Epidemiology 08/2012; 2012:191090. DOI:10.1155/2012/191090
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    • "0.7 [0.5–3.1] CDAI 234 [194–256] 327 [312–374] HBI 9 [7] [8] [9] [10] 12 [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] "
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    Scandinavian Journal of Gastroenterology 07/2011; 46(10):1206-14. DOI:10.3109/00365521.2011.603157 · 2.33 Impact Factor
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    • "FOXP3 may be transiently expressed in activated T cells, and its presence has also been reported in tumor cells (Ebert et al., 2008). Furthermore, FOXP3 is a nuclear protein, and its intracellular location limits its usefulness in Treg isolation, although it has often been applied to confirm the identity of Treg (Kryczek et al., 2009). "
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    Journal of immunological methods 06/2011; 369(1-2):59-68. DOI:10.1016/j.jim.2011.04.004 · 2.01 Impact Factor