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

Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE

Original Publication: [London] : Biomed Central, 2008-

Forkhead Transcription Factors/*biosynthesis ; Immunotherapy, Adoptive/*methods ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma, Experimental/*immunology ; Melanoma, Experimental/*therapy ; Receptors, Antigen, T-Cell/*genetics ; T-Lymphocytes/*immunology; Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/immunology ; Male ; Melanoma, Experimental/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/pathology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology

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 Foxp3(EGFP) mice. OT-II Foxp3(EGFP) 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 Foxp3(EGFP) 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.

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R01 AI085090 United States AI NIAID NIH HHS; T32 CA75956 United States CA NCI NIH HHS; R01 CA129816 United States CA NCI NIH HHS

0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
0 (Receptors, Antigen, T-Cell)

Date Created: 20111125 Date Completed: 20120523 Latest Revision: 20211021

20240829

PMC3245424

10.1186/1756-8722-4-48

22112546