CD24 Controls Expansion and Persistence of Autoreactive T Cells in the Central Nervous System during Experimental Autoimmune Encephalomyelitis

Bai, Xue‐Feng; Ou, Li; Zhou, Qunmin; Zhang, Huiming; Joshi, Pramod S.; Zheng, Xincheng; Liu, Yan; Wang, Yin; Zheng, Pan; Liu, Yang

doi:10.1084/jem.20040131

Cited by 87 publications

(100 citation statements)

References 35 publications

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“…Differences in the extent of infiltration by recipient-derived Thy1.2 ϩ T cells were especially notable in these two groups of recipients. The finding that many Thy1.2 ϩ IFN-␥ Ϫ/Ϫ lymphocytes migrated to the thyroids and contributed to L-SAT in the presence of WT lymphocytes is consistent with other reports demonstrating that host T cells could be recruited into inflammatory lesions by donor T cells (23). In contrast, very few recipient-derived Thy1.2 ϩ IFN-␥R Ϫ/Ϫ lymphocytes infiltrated the thyroids of IFN-␥R Ϫ/Ϫ mice given WT lymphocytes even though the IFN-␥R Ϫ/Ϫ lymphocytes could produce IFN-␥ (Fig.…”

Section: Discussionsupporting

confidence: 79%

Thyrocytes Responding to IFN-γ Are Essential for Development of Lymphocytic Spontaneous Autoimmune Thyroiditis and Inhibition of Thyrocyte Hyperplasia

Yu¹,

Sharp²,

Braley‐Mullen

2006

The Journal of Immunology

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IFN-γ promotes the development of lymphocytic spontaneous autoimmune thyroiditis (L-SAT) in NOD.H-2h4 mice and inhibits the development of thyrocyte hyperplasia and proliferation (TEC H/P). The precise mechanisms by which IFN-γ promotes L-SAT and inhibits TEC H/P are unknown. To determine whether responsiveness of lymphocytes or thyrocytes to IFN-γ is important for the development of these lesions, IFN-γR−/− mice, which develop TEC H/P similar to IFN-γ−/− mice, were used as recipients for adoptive cell transfer. Wild-type (WT) splenocytes or bone marrow induced L-SAT and inhibited TEC H/P in IFN-γ−/−, but not IFN-γR−/− recipients. IFN-γR−/− recipients of WT cells developed severe TEC H/P, but did not develop L-SAT, suggesting that thyrocytes responding to IFN-γ are important for inhibition of TEC H/P. Unexpectedly, IFN-γR−/− splenocytes or bone marrow did not induce L-SAT in IFN-γ−/− or WT mice even though IFN-γR−/− lymphocyte donors produced as much IFN-γ as lymphocytes from WT donors, and thyrocytes could respond to IFN-γ. Real-time PCR indicated that recipients of IFN-γR−/− bone marrow expressed less mRNA for IFN-γ-inducible chemokines compared with recipients of WT bone marrow. This might limit the migration of IFN-γR−/− lymphocytes to thyroids. Few IFN-γR−/− lymphocytes infiltrated thyroids even in the presence of WT lymphocytes, suggesting that lymphocytes unable to respond to IFN-γ are not induced to migrate to thyroids. These results suggest that thyrocytes must be able to respond to IFN-γ for the development of L-SAT and inhibition of TEC H/P, and lymphocytes must be able to respond to IFN-γ to induce L-SAT.

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Section: Discussionsupporting

confidence: 79%

Thyrocytes Responding to IFN-γ Are Essential for Development of Lymphocytic Spontaneous Autoimmune Thyroiditis and Inhibition of Thyrocyte Hyperplasia

Yu¹,

Sharp²,

Braley‐Mullen

2006

The Journal of Immunology

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“…70 Adoptive transfer studies revealed a critical role for CD24 on both T cells and radio-resistant host cells. 70,71 Furthermore, although pathogenic T cells can be recruited at comparable efficiency to the central nervous system of both wild-type and CD24-deficient mice, the T cells persist and expand only in the wild-type central nervous system. In vitro experiments demonstrated that the costimulatory activity of microglia and astrocytes from CD24-deficient mice is reduced.…”

Section: Cd24 and Autoimmune Diseasementioning

confidence: 99%

“…These data suggest that CD24 expressed on microglia and astrocytes may promote the activation and proliferation of pathogenic T cells. 71 Using transgenic mice with a glia-specific promoter, overexpression of CD24 in the central nervous system led to a more severe and progressive disease EAE. 72 The essential role of CD24 expression on T cells in experimental autoimmune encephalomyelitis is not understood.…”

Section: Cd24 and Autoimmune Diseasementioning

confidence: 99%

CD24: from A to Z

et al. 2010

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As a testament to the importance of CD24, researchers with diverse interests, including adaptive immunity, inflammation, autoimmune diseases and cancer, have encountered CD24. CD24 is overexpressed in many cancers and appears oncogenic. In the adaptive immune response, CD24 is a redundant costimulatory molecule in costimulation-rich lymphoid organs but is essential in selected target organs tested, such as brain and skin. More recent studies suggest it may have a role in discriminating danger and pathogen-associated molecular patterns by dendritic cells. The biology of CD24 is intriguing but poorly understood. Here we summarize the major findings associated with CD24 to stimulate new ideas for further research that may reveal the underlying link among the diverse processes mediated by CD24.

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“…Our recent studies suggest that CD24 expression is increased greatly in EAE lesions and CNS local cells close to the EAE lesion (our unpublished observation). Our previous studies have revealed that CD24 is required for the pathogenesis of EAE (19,22). The development of EAE requires CD24 expression on both T cells and non-T host cells.…”

Section: Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

CD24 on the Resident Cells of the Central Nervous System Enhances Experimental Autoimmune Encephalomyelitis

Liu

Carl

Joshi

et al. 2007

The Journal of Immunology

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CD24 is a cell surface glycoprotein that is expressed on both immune cells and cells of the CNS. We have previously shown that CD24 is required for the induction of experimental autoimmune encephalomyelitis (EAE), an experimental model for the human disease multiple sclerosis (MS). The development of EAE requires CD24 expression on both T cells and non-T host cells in the CNS. To understand the role of CD24 on the resident cells in the CNS during EAE development, we created CD24 bone marrow chimeras and transgenic mice in which CD24 expression was under the control of a glial fibrillary acidic protein promotor (AstroCD24TG mice). We showed that mice lacking CD24 expression on the CNS resident cells developed a mild form of EAE; in contrast, mice with overexpression of CD24 in the CNS developed severe EAE. Compared with nontransgenic mice, the CNS of AstroCD24TG mice had higher expression of cytokine genes such as IL-17 and demyelination-associated marker P8; the CNS of AstroCD24TG mice accumulated higher numbers of Th17 and total CD4+ T cells, whereas CD4+ T cells underwent more proliferation during EAE development. Expression of CD24 in CD24-deficient astrocytes also enhanced their costimulatory activity to myelin oligodendrocyte glycoprotein-specific, TCR-transgenic 2D2 T cells. Thus, CD24 on the resident cells in the CNS enhances EAE development via costimulation of encephalitogenic T cells. Because CD24 is increased drastically on resident cells in the CNS during EAE, our data have important implications for CD24-targeted therapy of MS.

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CD24 Controls Expansion and Persistence of Autoreactive T Cells in the Central Nervous System during Experimental Autoimmune Encephalomyelitis

Cited by 87 publications

References 35 publications

Thyrocytes Responding to IFN-γ Are Essential for Development of Lymphocytic Spontaneous Autoimmune Thyroiditis and Inhibition of Thyrocyte Hyperplasia

Thyrocytes Responding to IFN-γ Are Essential for Development of Lymphocytic Spontaneous Autoimmune Thyroiditis and Inhibition of Thyrocyte Hyperplasia

CD24: from A to Z

CD24 on the Resident Cells of the Central Nervous System Enhances Experimental Autoimmune Encephalomyelitis

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