IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-02-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3041759?pdf=render |
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| author | Mandana Zandian Kevin R Mott Sariah J Allen Shuang Chen Moshe Arditi Homayon Ghiasi |
| author_facet | Mandana Zandian Kevin R Mott Sariah J Allen Shuang Chen Moshe Arditi Homayon Ghiasi |
| author_sort | Mandana Zandian |
| collection | DOAJ |
| description | 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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| format | Article |
| id | doaj.art-507fa06662384e85b2e9ae36442fde91 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T05:11:44Z |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-507fa06662384e85b2e9ae36442fde912022-12-21T19:52:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1682010.1371/journal.pone.0016820IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination.Mandana ZandianKevin R MottSariah J AllenShuang ChenMoshe ArditiHomayon GhiasiTo 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.http://europepmc.org/articles/PMC3041759?pdf=render |
| spellingShingle | Mandana Zandian Kevin R Mott Sariah J Allen Shuang Chen Moshe Arditi Homayon Ghiasi IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination. PLoS ONE |
| title | IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination. |
| title_full | IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination. |
| title_fullStr | IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination. |
| title_full_unstemmed | IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination. |
| title_short | IL-2 suppression of IL-12p70 by a recombinant HSV-1 expressing IL-2 induces T-cell auto-reactivity and CNS demyelination. |
| title_sort | il 2 suppression of il 12p70 by a recombinant hsv 1 expressing il 2 induces t cell auto reactivity and cns demyelination |
| url | http://europepmc.org/articles/PMC3041759?pdf=render |
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