IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination.
IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination.
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DOI：
10.1371/journal.pone.0016820
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发表时间：
2011-02-18
期刊：
影响因子：
3.7
通讯作者：
Ghiasi H
中科院分区：
文献类型：
--
作者：
Zandian M;Mott KR;Allen SJ;Chen S;Arditi M;Ghiasi H
To evaluate the role of cellular infiltrates in CNS demyelination in immunocompetent mice, we have used a model of multiple sclerosis (MS) in which different strains of mice are infected with a recombinant HSV-1 expressing IL-2. Histologic examination of the mice infected with HSV-IL-2 demonstrates that natural killer cells, dendritic cells, B cells, and CD25 (IL-2rα) do not play any role in the HSV-IL-2-induced demyelination. T cell depletion, T cell knockout and T cell adoptive transfer experiments suggest that both CD8+ and CD4+ T cells contribute to HSV-IL-2-induced CNS demyelination with CD8+ T cells being the primary inducers. In the adoptive transfer studies, all of the transferred T cells irrespective of their CD25 status at the time of transfer were positive for expression of FoxP3 and depletion of FoxP3 blocked CNS demyelination by HSV-IL-2. The expression levels of IL-12p35 relative to IL-12p40 differed in BM-derived macrophages infected with HSV-IL-2 from those infected with wild-type HSV-1. HSV-IL-2-induced demyelination was blocked by injecting HSV-IL-2-infected mice with IL-12p70 DNA. This study demonstrates that suppression of the IL-12p70 function of macrophages by IL-2 causes T cells to become auto-aggressive. Interruption of this immunoregulatory axis results in demyelination of the optic nerve, the spinal cord and the brain by autoreactive T cells in the HSV-IL-2 mouse model of MS.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
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GALLO, P;PICCINNO, MG;TAVOLATO, B
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TAVOLATO, B
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Hemmer, B;Cepok, S;Sommer, N
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Sommer, N
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Wechsler, SL
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Chitnis, T;Najafian, N;Khoury, SJ
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