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. 2015 Sep 29;6:492. doi: 10.3389/fimmu.2015.00492

Table 1.

The protective effects of IFN-γ and IFN-γ-producing immune cells in EAE and MS.

Cell type Experimental design Effects of IFN-γ Reference
Macrophages In vitro culture of IFNGR-deficient PEC IFN-γ induces PEC NO-expression inhibiting proliferation of splenocytes (33)
Neutrophils Induced EAE in IFN-γ and IFNGR-deficient mice IFN-γ restricts neutrophils infiltration in the brainstem and cerebellum primarily by regulating CXCL2 expression (4042)
In vitro analysis of Gr1+ neutrophils sorted from CNS of mice with EAE IFN-γ secreted by T cells induced NO production by Gr1+ neutrophils which inhibited T cell proliferation (43)
Myeloid-derived suppressor cells (MDSCs) Analysis of CD11b+ Gr1+ MDSC from EAE mice IFN-γ secreted by activated T cells induced MDSC inhibiting CD4+ T cells proliferation by NO-dependent manner (44)
EAE mice treated with anti-IFN-γ Anti-IFN-γ reduced MDSCs frequency and increased EAE severity (45)
Natural killer cells (NK) EAE mice treated with anti-IFN-γ Decreased Th17-characteristic transcription factors expression due to modulation of microglia activation (46)
HINT1/Hsp70 protein complex from brains of PLP-sensitized SJL/J mice injected into congenic mice before immunization Upregulated MHC class I peptide H60 expression, increased NK cell IFN-γ production, inhibited IL-17 production, and prevented EAE (4749)
Analysis of NK cell functionality in human PBMC RRMS patients exhibit impaired response to IL-12 and severely diminished IFN-γ production in CD3CD56brightCD16 NK cells (50)
Invariant NKT cells In vivo IFN-γ neutralization in αGalCer-treated mice with EAE. In vitro iNKT analysis Increased production of IFN-γ, IL-4, and IL-10 by iNKT cells which mediated the suppression of Th17 cells and increased EAE regulation by MDSCs (5153)
Dendritic cells (DC) Transfer of IFN-γ treated DC into murine EAE models Induced an incompletely mature DC phenotype and decreased disease severity and relapse frequency (54)
In vitro analysis of splenocytes isolated from WT and IFN-γ-deficient EAE mice Induced DC IL-27 expression which inhibited Th9 cell differentiation and IL-9 production by Th9 and Th17 cells (55)
CD4+ T lymphocytes IFN-γ added to CD3-activated PBMC from chronic-progressive MS patients Lymphocyte proliferation inhibition in an IFN-γ dose-dependent manner (56)
Analysis of IFN-γ deficient mice with EAE Increased apoptosis and inhibited proliferation in vivo and ex vivo of CD4+CD44high T cells in spleen and CNS (57)
Study of IFN-γ and IFNGR EAE deficient mice Inhibited Th17 differentiation and IL-17 production (31, 5862)
IFN-γ deficient EAE mice treated with anti-IL-9 Decreased Th9 differentiation and IL-9 production in vitro and in vivo in the CNS of mice with EAE (55)
CD4+ T cells transfected with IFN-γ expressing vector transferred into EAE mice Th1 IFN-γhighCD25FOXP3 suppresses Th17 effector cells and decreased EAE severity (63)
γδ T cells EAE generated in bone marrow chimera with γδ and IFN-γ-deficient mice γδ T cells promotes the expression of IFN-γ by T cells with a reduction of EAE severity (64)
CD4+ Tregs In vitro addition of IFN-γ to mice and human CD4+CD25 T cell cultures. IFN-γ-converted Tregs injected into EAE mice IFN-γ-converted Tregs inhibited T cell proliferation in mice and human cells. Administration of these cells ameliorated EAE severity (65)
CD8+ T lymphocytes Transfer of MOG-induced CD8+ T cells from IFN-γ-deficient mice into wild-type mice before EAE induction Amelioration of EAE severity mediated by CD8+ T cell IFN-γ production (66)
Analysis of CD8+LAP+ T cells from IFN-γ and IFNGR-deficient mice and transfer into EAE IFN-γ production by CD8+LAP+ T cells inhibited T cell proliferation and reduced severity of EAE. (67)
Vaccination with a TCR-derived peptide before EAE induction in WT and IFN-γ KO mice Vaccination activates CD8αα+TCRαβ+ T cells and delayed EAE onset in an IFN-γ mediated fashion (6870)
Isolation of human and mice CD8+CD38high T cells. In vivo injection of CD8+CD38high into EAE mice IFN-γ production by CD8+CD38high T cells inhibit T cell proliferation in human and mice. These cells decreased disease severity and delayed onset of EAE. (71)
MS patients and EAE mice treated with Glatiramer acetate (GA) GA increases CD8+ T proliferation and IFN-γ levels in MS and IDO and IFN-γ-producing CD8+ T cells in EAE (72, 73)
B cells IFN-γ treatment in early EAE stage in marmoset Reduced plasma MOG-specific IgG levels (35)
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