Abstract |
Immunization with serological identification of Ags by recombinant expression cloning (SEREX)-defined self-Ags leads to generation/activation of CD4+ CD25+ regulatory T cells with suppressive activities and enhanced expression of Foxp3. This is associated with increased susceptibility to pulmonary metastasis following challenge with syngeneic tumor cells and enhanced development of 3-methylcholanthrene-induced primary tumors. In contrast, coimmunization with the same SEREX-defined self-Ags mixed with a CTL epitope results in augmented CTL activity and heightened resistance to pulmonary metastasis, both of which depend on CD4+ Th cells. These active regulatory T cells and Th cells were derived from two distinct CD4+ T cell subsets, CD4+ CD25+ T cells and CD4+ CD25- T cells, respectively. In the present study, IFN-gamma was found to abrogate the generation/activation of CD4+ CD25+ regulatory T cells by immunization with SEREX-defined self-Ag. CD4+ CD25+ T cells from these IFN-gamma-treated mice failed to exhibit immunosuppressive activity as measured by 1) increased number of pulmonary metastasis, 2) enhanced development of 3-methylcholanthrene-induced primary tumors, 3) suppression of peptide-specific T cell proliferation, and 4) enhanced expression of Foxp3. The important role of IFN-gamma produced by CD8+ T cells was shown in experiments demonstrating that CD4+ CD25+ T cells cotransferred with CD8+ T cells from IFN-gamma(-/-) mice, but not from wild-type BALB/c mice, became immunosuppressive and enhanced pulmonary metastasis when recipient animals were subsequently immunized with a SEREX-defined self-Ag and a CTL epitope. These findings support the idea that IFN-gamma regulates the generation/activation of CD4+ CD25+ regulatory T cells.
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Authors | Hiroyoshi Nishikawa, Takuma Kato, Isao Tawara, Hiroaki Ikeda, Kagemasa Kuribayashi, Paul M Allen, Robert D Schreiber, Lloyd J Old, Hiroshi Shiku |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 175
Issue 7
Pg. 4433-40
(Oct 01 2005)
ISSN: 0022-1767 [Print] United States |
PMID | 16177085
(Publication Type: Journal Article)
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Chemical References |
- Epitopes
- Heat-Shock Proteins
- Receptors, Interleukin-2
- Interferon-gamma
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Topics |
- Animals
- Cell Line, Tumor
- Cells, Cultured
- Epitopes
(immunology)
- Female
- Heat-Shock Proteins
(immunology)
- Interferon-gamma
(deficiency, genetics, physiology)
- Lung Neoplasms
(immunology, prevention & control, secondary)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Mice, SCID
- Mice, Transgenic
- Receptors, Interleukin-2
(biosynthesis, metabolism)
- Sarcoma, Experimental
(immunology, pathology, prevention & control)
- T-Lymphocyte Subsets
(immunology)
- T-Lymphocytes, Cytotoxic
(immunology)
- T-Lymphocytes, Regulatory
(immunology)
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