Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity

Slavin, Anthony; Soos, Jeanne M.; Stüve, Olaf; Patarroyo, Juan C.; Weiner, Howard L.; Fontana, A.; Bikoff, Elizabeth K.; Zamvil, Scott S.

doi:10.1172/jci200113360

Cited by 52 publications

(69 citation statements)

References 35 publications

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“…Our results extend the notion of the CNS as an environment that triggers initial T cell activation and clonal expansion to include the triggering of Tregs. There is clear evidence that, during the course of EAE, CNS-resident DCs efficiently process and present CNS-derived Ags (28,29) (30). It is also known that mature DCs can efficiently stimulate the proliferation of Tregs (25,31), and so it seems likely that DCs infiltrating the inflamed CNS promote the expansion of Tregs in situ.…”

Section: Discussionmentioning

confidence: 99%

The Inflamed Central Nervous System Drives the Activation and Rapid Proliferation of Foxp3+ Regulatory T Cells

O’Connor

Malpass

Anderton

2007

The Journal of Immunology

152

162

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Section: Discussionmentioning

confidence: 99%

The Inflamed Central Nervous System Drives the Activation and Rapid Proliferation of Foxp3+ Regulatory T Cells

O’Connor

Malpass

Anderton

2007

The Journal of Immunology

152

162

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“…The Ag specificity of conventional ␣␤ T cells and the presence of their restriction element are essential for their recruitment to or retention within the CNS, as well as their local reactivation (43)(44)(45)(46). To determine whether CD1d Ag presentation exerts a similar selective pressure on CNS-infiltrating NKT cells, we assessed their frequency, subset composition, and effector phenotype in the different mouse lines 15 days after immunization (Fig.…”

Section: Cns-infiltrating Nkt Cells Are Predominantly Double Negativementioning

confidence: 99%

Invariant NKT Cells Regulate Experimental Autoimmune Encephalomyelitis and Infiltrate the Central Nervous System in a CD1d-Independent Manner

Mars

Gautron

Novák

et al. 2008

The Journal of Immunology

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Invariant NKT cells are CD1d-restricted T cells specific for glycolipid Ags. Their activation or transgenic enrichment abrogates the development of experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate that in NKT-enriched mice the protection from EAE is associated with the infiltration of NKT cells in the CNS and the local expression of CD1d. This indicates that the CNS acquires the potential for local glycolipid presentation when exposed to inflammatory stress, permitting the triggering of NKT cells. To address the importance of CD1d-mediated Ag presentation, we used transgenic mice that express CD1d solely in the thymus. Interestingly, enrichment of NKT cells in these mice also conferred resistance to EAE, with an efficacy indistinguishable from that of NKT-enriched CD1d-sufficient mice. This protection was due to an abrogation of the encephalitogenic Th1 and Th17 response in the spleen, revealing that endogenous glycolipid presentation is dispensable for the regulatory function of NKT cells in EAE. Moreover, abrogating extrathymic CD1d expression failed to affect both the recruitment of NKT cells and their effector phenotype. CNS-infiltrating NKT cells were characterized by a cytotoxic IFN-γhighIL-4lowIL-10lowgranzyme Bhigh profile, irrespective of the local expression of CD1d. Glycolipid Ag presentation is therefore dispensable for the control of autoimmune demyelination by NKT cells, underlining the importance of alternative cognate and/or soluble factors in the control of NKT cell function.

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“…The significance of myelin-specific antibodies in mediating myelin loss in this EAE model is controversial (Lalive, 2008). As only B cell receptor (BCR) binding by native antigens initiates BCR signaling and a program of B-cell activation that ultimately results in B-cell differentiation and antibody production, it has generally been considered that production of MOG autoantibodies does not to take place in MOG 35-55 -induced EAE in a meaningful manner (Slavin et al, 2001). A small body of evidence however points to a possible contribution of myelin-reactive antibodies to MOG 35-55 -induced EAE pathogenesis, and in particular T cell-dependent IgG1 and IgG2a antibody responses (Zhang et al, 2004); first, the benefit of B cell-depletion in MOG-induced EAE was associated with decreased antibody titers against MOG peptide (Matsushita et al, 2006); second, transfer of anti-MOG serum from MOG 35-55 -immunized mice has been demonstrated to increase severity of EAE in WT mice (Du and Sriram, 2002).…”

Section: Introductionmentioning

confidence: 99%

Antibody response in MOG35–55 induced EAE

Lalive

Molnarfi

Benkhoucha

et al. 2011

Journal of Neuroimmunology

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Neurological deficit in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis is widely considered to be a consequence of synergistic T and B cell responses to central nervous system (CNS) antigens. We show that mice immunized with encephalitogenic myelin oligodendrocyte glycoprotein ) peptide develop significant serum levels of anti-MOG antibodies in parallel with disease progression. Furthermore, EAE mice developed antibodies against DNA and RNA, a serological hallmark observed in autoimmune diseases such as systemic lupus erythematosus. The presence of anti-nucleic responsive B cells and antibodies during EAE may highlight a previously unappreciated mechanism in the pathogenesis of CNS autoimmunity.

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Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity

Cited by 52 publications

References 35 publications

The Inflamed Central Nervous System Drives the Activation and Rapid Proliferation of Foxp3+ Regulatory T Cells

The Inflamed Central Nervous System Drives the Activation and Rapid Proliferation of Foxp3+ Regulatory T Cells

Invariant NKT Cells Regulate Experimental Autoimmune Encephalomyelitis and Infiltrate the Central Nervous System in a CD1d-Independent Manner

Antibody response in MOG35–55 induced EAE

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