CD1-Dependent Regulation of Chronic Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis

Teige, Anna; Teige, Ingrid; Lavasani, Shahram; Bockermann, Robert; Mondoc, Emma; Holmdahl, Rikard; Issazadeh‐Navikas, Shohreh

doi:10.4049/jimmunol.172.1.186

Cited by 56 publications

(49 citation statements)

References 66 publications

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“…CD1d is known to stimulate a subset of T cells with postulated immunoregulatory functions in EAE and MS (67)(68)(69), and we have shown that mice deficient in CD1d develop augmented and a more chronic EAE (30). Interestingly, we found that both IFNs increased expression of CD1d on astrocytes and microglia.…”

Section: Discussionsupporting

confidence: 53%

“…We also investigated the expression of the nonclassical MHC-like molecule CD1d because we have reported that this molecule plays a crucial role in the regulation of CNS inflammation (30). Interestingly, we found that both astrocytes and microglia express relatively high levels of CD1d and this was elevated by IFN-␤ as well as by IFN-␥ (Fig.…”

Section: Ifn-␤ and Ifn-␥ Elevate Cd1d Expression On Glial Cellsmentioning

confidence: 73%

“…Draining lymph nodes were collected day 10 postimmunization and the cells went through several rounds of Ag-specific restimulation as described (30). This generated T cell lines of the Th1 phenotype that produced large amounts of IFN-␥ and IL-2 and very low amounts of IL-4 upon Ag stimulation.…”

Section: Establishment Of Myelin-specific T Cell Linesmentioning

confidence: 99%

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IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Teige

Liu

Issazadeh‐Navikas

2006

The Journal of Immunology

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We have previously investigated the physiological effects of IFN-β on chronic CNS inflammation and shown that IFN-β−/− mice develop a more severe experimental autoimmune encephalomyelitis than their IFN-β+/− littermates. This result was shown to be associated with a higher activation state of the glial cells and a higher T cell cytokine production in the CNS. Because this state suggested a down-regulatory effect of IFN-β on CNS-specific APCs, these results were investigated further. We report that IFN-β pretreatment of astrocytes and microglia (glial cells) indeed down-modulate their capacity to activate autoreactive Th1 cells. First, we investigated the intrinsic ability of glial cells as APCs and report that glial cells prevent autoreactive Th1 cells expansion while maintaining Ag-specific T cell effector functions. However, when the glial cells are treated with IFN-β before coculture with T cells, the effector functions of T cells are impaired as IFN-γ, TNF-α, and NO productions are decreased. Induction of the T cell activation marker, CD25 is also reduced. This suppression of T cell response is cell-cell dependent, but it is not dependent on a decrease in glial expression of MHC class II or costimulatory molecules. We propose that IFN-β might exert its beneficial effects mainly by reducing the Ag-presenting capacity of CNS-specific APCs, which in turn inhibits the effector functions of encephalitogenic T cells. This affect is of importance because activation of encephalitogenic T cells within the CNS is a prerequisite for the development of a chronic progressive CNS inflammation.

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Section: Discussionsupporting

confidence: 53%

Section: Ifn-␤ and Ifn-␥ Elevate Cd1d Expression On Glial Cellsmentioning

confidence: 73%

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IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Teige

Liu

Issazadeh‐Navikas

2006

The Journal of Immunology

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“…iNKT cells are abundant in the liver and rapidly secrete large amounts of immunoregulatory cytokines such as IFN-g and IL-4 after stimulation through their TCR [35][36][37][38][39][40]. Administration of a-GalCer to mice causes rapid release of various cytokines from iNKT cells, which participate in the regulation of various diseases, including tumor rejection and prevention of autoimmune diseases [41][42][43][44][45][46].Although a-GalCer can enhance host resistance against some microbial pathogens [47-55], it remains elusive whether a-GalCer enhances protective immunity against intracellular bacteria.We have recently shown that listeriosis is ameliorated in iNKT-cell-deficient mice [56]. This finding argues against a protective role of iNKT cells in listeriosis.…”

mentioning

confidence: 99%

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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a-Galactosylceramide (a-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by a-GalCer. Here, we show that a-GalCer treatment ameliorates murine listeriosis, and inhibits inflammation following Listeria monocytogenes infection. Liver infiltration of Gr-1 1 cells and c/d T cells was accelerated by a-GalCer treatment. Gr-1 1 cell and c/d T-cell depletion exacerbated listeriosis in a-GalCer-treated mice, and this effect was more pronounced after depletion of Gr-1 1 cells than that of c/d T cells. Although GM-CSF and IL-17 were secreted by NKT cells after a-GalCer treatment, liver infiltration of Gr-1 1 cells was not prevented by neutralizing mAb. In parallel to the numerical increase of CD11b 1 Gr-1 1 cells in the liver following a-GalCer treatment, CD11b À Gr-1 1 cells were numerically reduced in the bone marrow. In addition, respiratory burst in Gr-1 1 cells was enhanced by a-GalCer treatment. Our results indicate that a-GalCer-induced antibacterial immunity is caused, in part, by accelerated infiltration of Gr-1 1 cells and to a lesser degree of c/d T cells into the liver. We also suggest that the infiltration of Gr-1 1 cells is caused by an accelerated supply from the bone marrow.Key words: a-galactosylceramide . L. monocytogenes . NKT cell Supporting Information available online IntroductionListeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen, which causes disseminated infection in immunocompromised hosts [1]. Experimental murine listeriosis is instrumental in elucidating host defense mechanisms against intracellular bacteria. Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes [2-5] and among these, Gr-1 1 cells are central for the elimination of this pathogen at early stages of infection [6][7][8]. Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10]. G-CSF is indispensable for both steady-state and emergency granulopoiesis [11][12][13][14], and IL-17 regulates G-CSF secretion [9,10,[15][16][17][18]. In addition to Gr-1 1 cells, g/d T cells also participate in early protection against 1328L. monocytogenes infection [19][20][21][22]. The vast majority of L. monocytogenes organisms are trapped in the liver immediately after systemic infection [23] and hence, immunocompetent cells that reside in, and/or migrate into, the liver are critical for infection control.NKT cells represent a unique subset of T lymphocytes, which are characterized by the co-expression of NK cell markers such as NKR-P1B/C (NK1.1; CD161) [24]. In the mouse, the majority of NKT cells express an invariant (i) TCR composed of Va14/Ja18 gene segments, i.e. iNKT cells [24]. In contrast to conventional T cells, which recognize peptide antigens presented by polymorphic MHC ...

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“…Upon activation, NKT cells produce a large amount of both IFN-␥ and IL-4, which can modulate the immune responses to certain diseases, especially to autoimmune diseases, or infections (7)(8)(9)(10)(11)(12)(13).…”

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confidence: 99%

α-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor

Chang

et al. 2005

The Journal of Immunology

165

124

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α-Galactosylceramide (α-GalCer) is a ligand of invariant Vα14+ NKT cells and is presented by CD1d molecule on APC. NKT cells produce a large amount of Th1 and Th2 cytokines in response to α-GalCer-presented APC. In this study, we assessed whether α-GalCer could act as an effective nasal vaccine adjuvant for mucosal vaccine that would be capable of inducing systemic as well as mucosal immune responses. When α-GalCer was administered with OVA via the intranasal route to C57BL/6 and BALB/c mice, significant OVA-specific mucosal secretory IgA, systemic IgG, and CTL responses were induced with mixed Th1 and Th2 cytokine profiles seen in both strains of mice. Interestingly, as BALB/c mice were intranasally immunized with PR8 hemagglutinin Ag isolated from influenza virus A/PR/8/34 together with α-GalCer, significant protection was afforded against influenza viral infection. When α-GalCer was coimmunized with a replication-deficient live adenovirus to BALB/c mice, it significantly induced both humoral and cellular immune responses. In addition, intranasal administration of OVA with α-GalCer showed complete protection against EG7 tumor challenge in C57BL/6. The adjuvant effects induced by intranasal coadministration with α-GalCer were blocked in CD1d−/− mice, indicating that the immune responses were exclusively mediated by CD1d molecule on APC. Most interestingly, intranasally coadministered α-GalCer activated naive T cells and triggered them to differentiate into functional effector T cells when CFSE-labeled OT-1 cells were adoptively transferred into syngeneic mice. Overall, our results are the first to show that α-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors.

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CD1-Dependent Regulation of Chronic Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis

Cited by 56 publications

References 66 publications

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

α-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor

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CD1-Dependent Regulation of Chronic Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis

Cited by 56 publications

References 66 publications

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

IFN-β Inhibits T Cell Activation Capacity of Central Nervous System APCs

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

α-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor

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Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver