Purchase this article with an account.
O. M. Dumitrascu, K. Mott, M. Zandian, S. Allen, R. Kumar, B. T. Rouse, D. Gate, T. Town, H. Ghiasi; Regulatory T Cells Induce CNS Autoimmunity After HSV-1 Infection in the Absence of IL-12p70 Macrophage Signaling. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3810.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of innate and adaptive immunity in CNS demyelination in mice ocularly infected with different strains of HSV-1.
Effect of macrophages, DCs, NK cells, B cells, or T cells on CNS demyelination in female BALB/c or C57BL/6 mice following ocular infection with virulent HSV-1 strain McKrae, avirulent HSV-1 strain KOS, or a LAT- and γ-34.5-minus virus was determined at various times post infection by Luxol Fast Blue (LFB). Demyelination in IL-12p35-/-, IL-12p40-/-, IL-23p19-/-, and EBI3-/- was determined in infected mice by LFB. Contributions of T cells to CNS demyelination in the absence of macrophages and protection from CNS demyelination in macrophage-depleted mice injected with IL-12p70 DNA was determined in infected mice by LFB and IHC for HSV-1, GFAP, CD11b, and F4/80.
Our results suggest that depletion of macrophages but not DCs, B-cells, NK cells, CD4+ T cells, CD8+ T cells, or both T cells induced CNS demyelination irrespective of virus or mice strain that was used. Similar to macrophage depletion, both IL-12p35-/- and IL-12p40-/- mice showed CNS demyelination following ocular infection, while no demyelination was detected in IL-23p19-/- or IL-35EBI3-/- infected mice. Demyelination was blocked in macrophage depleted mice following injection of IL-12p70 DNA. Similarly, demyelination in IL-12p35-/- or IL-12p40-/- mice was blocked following injection of these mice with IL-12p35 or IL-12p40 DNA or recombinant viruses expressing IL-12p35 or IL-12p40, respectively. Using CD4, CD8, and CD25 depletions and their knockout mice we have shown that demyelination was blocked in the absence of CD4 or CD25. FACS analyses shown elevation of CD4+CD25+FOXP3+ T cells in spleen of macrophage depleted and infected mice. Adoptive transfer of CD4+CD25+ T cells to macrophage-depleted SCID mice induced CNS demyelination in infected recipient mice.
In this study for the first time we have shown that macrophages play an important role in maintaining immune balance in the CNS by preventing the CD4 Tregs from becoming auto-reactive via their IL-12p70 function.
This PDF is available to Subscribers Only