Title: TGFbeta1 deficiency does not affect the generation and maintenance of CD4+CD25+FOXP3+ putative Treg cells, but causes their numerical inadequacy and loss of regulatory function.
Authors: Bommireddy, Ramireddy; Babcock, George F; Singh, Ram R; Doetschman, Thomas
Published In Clin Immunol, (2008 May)
Abstract: TGFbeta1 is considered to be required for peripheral maintenance of CD4(+)CD25(+)FOXP3(+) T(reg) cells. However, we demonstrate no reduction in the percentage of such T cells in the spleens and thymi of Tgfb1(-/-) mice. Although putative T(reg) cells, characterized as CD4(+)CD25(+)FOXP3(+)CD62L(+) T cells, are increased in Tgfb1(-/-) mice, they may be inadequate to control activated T cells since the ratio of activated T cells:putative T(reg) cells is several-fold higher in Tgfb1(-/-) mice than in control mice. We further show that whereas Tgfb1(-/-) mice that express a chicken OVA-specific TCR transgene (DO11.10) have an increase in putative T(reg) cells, there are no detectable CD4(+)CD25(+) T cells in the spleens of DO11.10 Rag1(-/-) mice suggesting that T(reg)-cell generation is self-antigen dependent regardless of whether they express Tgfb1. Finally, we demonstrate that Tgfb1(-/-) T cells remain responsive to the suppressive effect of TGFbeta1 in vitro. These data suggest that TGFbeta1 is required for the regulatory function of T(reg) cells to prevent activation of T cells and autoimmunity.
PubMed ID:
18308639
MeSH Terms: Animals; Antigens, CD/immunology; Antigens, Differentiation, T-Lymphocyte/immunology; Autoimmunity/immunology; Cell Proliferation; Flow Cytometry; Forkhead Transcription Factors/immunology*; Immune Tolerance/immunology*; L-Selectin/immunology; Lectins, C-Type; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Phenotype; Spleen/cytology; Spleen/immunology; T-Lymphocytes, Regulatory/cytology; T-Lymphocytes, Regulatory/immunology*; Thymus Gland/cytology; Thymus Gland/immunology; Transforming Growth Factor beta1/genetics; Transforming Growth Factor beta1/immunology*