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In vitro and in vivo activation of CD4+CD25−Foxp3+ Tregs in NZB/W mice
Author(s) -
Scalapino Kenneth John,
Daikh David I
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1073.13
Subject(s) - il 2 receptor , foxp3 , in vivo , cd28 , in vitro , immunology , biology , t cell , immune system , biochemistry , genetics
PURPOSE: CD4 + Foxp3 + T regs increase with onset of lupus in (NZBxNZW)F 1 (B/W) mice, but many T regs lack CD25 expression. Absence of CD25 is correlated with impaired T reg function. The ability to restore CD25 expression and enhance T reg function was assessed. METHODS: CD4 + CD25 − CD62L LO T cells were stimulated with anti‐CD3/anti‐CD28 and IL‐2. Cells up‐regulating CD25 were sorted and tested for Foxp3 expression, suppression capacity, and survival. In vivo up‐regulation of CD25, Foxp3, and suppression capacity following a brief course of IL‐2 to mice was then assessed. RESULTS: 44% of T regs in sick B/W mice were CD4 + CD25 − CD62L LO . Stimulation of these cells in vitro resulted in up‐regulation of CD25 on 85% of T regs . Activated T regs expressed high levels of CD25, Foxp3, and had enhanced in vitro suppression and in vivo survival following adoptive transfer. Activation of CD4 + CD25 − T regs in vivo by IL‐2 increased per cell Foxp3 expression and the fraction of T regs that were CD25 + (75%). Purified CD4 + CD25 + T cells from treated mice were highly suppressive when tested in vitro . CONCLUSION: Inadequate CD25 expression on B/W T regs may correlate with impaired T reg function and disease development. This problem is reversible, producing T regs with prolonged survival and suppression capacity. These results suggest the potential for lupus therapies directed towards T reg activation. Supported by Department of Veterans Affairs.