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Open Access Research

T cell receptor transgenic lymphocytes infiltrating murine tumors are not induced to express foxp3

Jon G Quatromoni1, Lilah F Morris1, Timothy R Donahue1, Yue Wang1, William McBride2, Talal Chatila3 and James S Economou145*

Author Affiliations

1 Departments of Surgery, University of California, Los Angeles, 10833 Le Conte Avenue Room 54-140 CHS Los Angeles, CA 90095 USA

2 Radiation Oncology, University of California, 10833 Le Conte Avenue, Room B3-109 CHS Los Angeles, CA 90095 USA

3 Pediatrics, University of California, 805 Tiverton, Room 12-430 Marion Davies Children's Center, Los Angeles, CA 90095 USA

4 Microbiology, Immunology and Molecular Genetics+, University of California, Los Angeles, 10833 Le Conte Avenue, Room 54-140 CHS, Los Angeles, CA 90095 USA

5 Molecular and Medical Pharmacology, University of California, 10833 Le Conte Ave, 54-140 CHS, Los Angeles, CA 90095 USA

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Journal of Hematology & Oncology 2011, 4:48  doi:10.1186/1756-8722-4-48

Published: 23 November 2011

Abstract

Regulatory T cells (Treg) that express the transcription factor Foxp3 are enriched within a broad range of murine and human solid tumors. The ontogeny of these Foxp3 Tregs - selective accumulation or proliferation of natural thymus-derived Treg (nTreg) or induced Treg (iTreg) converted in the periphery from naïve T cells - is not known. We used several strains of mice in which Foxp3 and EGFP are coordinately expressed to address this issue. We confirmed that Foxp3-positive CD4 T cells are enriched among tumor-infiltrating lymphocytes (TIL) and splenocytes (SPL) in B16 murine melanoma-bearing C57BL/6 Foxp3EGFP mice. OT-II Foxp3EGFP mice are essentially devoid of nTreg, having transgenic CD4 T cells that recognize a class II-restricted epitope derived from ovalbumin; Foxp3 expression could not be detected in TIL or SPL in these mice when implanted with ovalbumin-transfected B16 tumor (B16-OVA). Likewise, TIL isolated from B16 tumors implanted in Pmel-1 Foxp3EGFP mice, whose CD8 T cells recognize a class I-restricted gp100 epitope, were not induced to express Foxp3. All of these T cell populations - wild-type CD4, pmel CD8 and OTII CD4 - could be induced in vitro to express Foxp3 by engagement of their T cell receptor (TCR) and exposure to transforming growth factor β (TGFβ). B16 melanoma produces TGFβ and both pmel CD8 and OTII CD4 express TCR that should be engaged within B16 and B16-OVA respectively. Thus, CD8 and CD4 transgenic T cells in these animal models failed to undergo peripheral induction of Foxp3 in a tumor microenvironment.