| Abstract: |
Immunization with serological identification of Ags by recombinant expression cloning (SEREX)-deflned self-Ags leads to generation/activation of CD4 +CB25 + 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-γ was found to abrogate the generation/activation of CD4 +CD25 + regulatory T cells by immunization with SEREX-deflned self-Ag. CD4 +CD25 + T cells from these IFN-γ-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-γ produced by CD8 + T cells was shown in experiments demonstrating that CD4 +CB25 + T cells cotransferred with CD8 + T cells from IFN-γ -/- 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-γ regulates the generation/activation of CD4 +CD25 + regulatory T cells. Copyright © 2005 by The American Association of Immunologists, Inc. |
| Keywords: |
controlled study; nonhuman; transcription factor foxp3; lymphocyte proliferation; t lymphocyte; mouse; animals; mice; mice, knockout; cells, cultured; lung neoplasms; animal experiment; animal model; antineoplastic activity; mice, scid; cell line, tumor; mice, inbred balb c; mice, transgenic; lung metastasis; immune response; gamma interferon; t-lymphocytes, regulatory; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; tumor immunity; t-lymphocyte subsets; cd4 antigen; immunosuppressive treatment; serology; t lymphocyte activation; interleukin 2 receptor alpha; immunization; epitopes; receptors, interleukin-2; sarcoma, experimental; heat-shock proteins; interferon type ii; 3 methylcholanthrene
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