Autoantibody production in lpr/lpr gld/gld mice reflects accumulation of CD4+ effector cells that are resistant to regulatory T cell activity
| Autor: | Brian D. Hondowicz, Simone A. Nish, Jan Erikson, Andrew J. Caton, Joseph Larkin, Michele L. Fields |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Adoptive cell transfer Mice Inbred MRL lpr Regulatory T cell Lymphocyte T cell Immunology Population chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Article Interferon-gamma Mice T-Lymphocyte Subsets medicine Immunology and Allergy Animals education Interleukin 4 Autoantibodies education.field_of_study B-Lymphocytes Mice Inbred BALB C FOXP3 hemic and immune systems Forkhead Transcription Factors T lymphocyte Adoptive Transfer Mice Mutant Strains medicine.anatomical_structure Female Interleukin-4 |
| Zdroj: | Journal of autoimmunity. 31(2) |
| ISSN: | 0896-8411 |
| Popis: | In Fas/FasL-deficient mice anti-chromatin Ab production is T cell dependent and is not apparent until after 10 weeks of age. Early control of anti-chromatin antibodies may be due to the counterbalancing influence of Treg cells. Here we show that Treg cells block lpr/lpr gld/gld Th cells from providing help to anti-chromatin B cells in an in vivo transfer system. Interestingly, the percentage and absolute numbers of Foxp3 + Treg cells is elevated in BALB/c- lpr/lpr gld/gld mice and increases with age compared to BALB/c mice. The majority of Foxp3 expression is found in the B220 − CD4 + T cell population, and Foxp3-expressing cells are localized in the splenic PALS (periarteriolar lymphocyte sheath). Strikingly, although the lack of functional Fas/FasL does not affect the ability of Treg cells to block Th cell proliferation, Treg cells can block the IFN-γ differentiation of Th cells from BALB/c or young BALB- lpr/lpr gld/gld mice but not of pre-existing Th1 cells from older BALB/c- lpr/lpr gld/gld mice. Thus, we suggest autoantibody production is not caused by the lack of Treg cells but by a defect in activation-induced cell death that leads to the accumulation of T effector cells that are resistant to regulatory T cell activity. |
| Databáze: | OpenAIRE |
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