Efficacy of Synthetic Peptide Corresponding to the ACTH-Like Sequence of Human Immunoglobulin G1 in Experimental Autoimmune Encephalomyelitis

Turobov, V. I.; Danilkovich, Alexey; Шевелев, А. Б.; Бирюкова, Ю. К.; Позднякова, Н. В.; Азев, В. Н.; Мурашев, А. Н.; Липкин, В. М.; Udovichenko, Igor P.

doi:10.3389/fphar.2018.00113

Cited by 3 publications

(3 citation statements)

References 26 publications

(28 reference statements)

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“…Multiple sclerosis (MS) is an autoimmune disease that occurs in central nervous system (CNS). [1] Unfortunately, current therapies of MS are based on non-specific immunosuppressive drugs, such as natalizumab, fingolimod, mitoxantrone, and dimethyl fumarate, which have many side effects. [1,2] The pathogenesis of MS is mediated primarily by T cells that are activated by CNS autoantigens and finally damage the myelin sheath to generate active lesions in the CNS.…”

Section: Introductionmentioning

confidence: 99%

“…[1] Unfortunately, current therapies of MS are based on non-specific immunosuppressive drugs, such as natalizumab, fingolimod, mitoxantrone, and dimethyl fumarate, which have many side effects. [1,2] The pathogenesis of MS is mediated primarily by T cells that are activated by CNS autoantigens and finally damage the myelin sheath to generate active lesions in the CNS. [3] Typically, studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4 + T cells, which is induced by myelin antigens (aEAE) or adoptive transfer of myelin-reactive T cells (tEAE).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of myelin oligodendrocyte glycoprotein (MOG)35–55-specific CD8+ T cells in experimental autoimmune encephalomyelitis

Peng

Zhu

Chen

et al. 2019

Chinese Medical Journal

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Background: The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4 + T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE. Methods: Female C57BL/6 mice (n = 20) were induced by myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4 + and CD8 + T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG 35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-g) and interleukin (IL)-4 secretion of supernatant of cultured CD4 + and CD8 + T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG 35-55 -specific CD8 + or CD4 + T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining. Results: CD8 + CD3 + and CD4 + CD3 + cells were 86% and 94% pure of total CD3 + cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG 35-55 peptide and applied to proliferation assays. Although the CD8 + T cells had a generally lower response to MOG 35-55 than CD4 + T cells, the response of CD8 + T cells was not always dependent on CD4. CD8 + T cell secreted less IFN-g and IL-4 compared with CD4 + T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG 35-55 -specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 + T cells from immunized B6 mice compared with transfer of CD4 + T cells. Conclusion: Our data suggest that CD8 + autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4 + counterparts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of myelin oligodendrocyte glycoprotein (MOG)35–55-specific CD8+ T cells in experimental autoimmune encephalomyelitis

Peng

Zhu

Chen

et al. 2019

Chinese Medical Journal

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“…MCM on MS are non-speci c immunosuppressive drugs, which remains many side effects. [15] Typically, studies of MS and EAE have focused on CD4 + T cells, however, CD8 + T cells are involved in MS/EAE pathogenesis. [16] As we reported previously, myelin oligo-dendrocyte glycoprotein (MOG) 35−55 -speci c CD4 + and CD8 + autoreactive T cells from B6 EAE mouse were encephalitogenic, and our previous data already showed that CD8 + T cells were unique and independent on pathogenic of EAE rather than their CD4 + counterparts.…”

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confidence: 99%

Experimental autoimmune encephalomyelitis inhibited by Huangqi Guizhi Wuwu Decoction by enhancing Th2 cytokine

Peng¹,

Zhu²,

Zhou³

et al. 2020

Preprint

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Background: Current modern conventional medicine (MCM) on multiple sclerosis (MS) are non-specific immunosuppressive drugs, which remains many side effects. Huangqi Guizhi Wuwu decoction (HQGZWW) is a common formula of Chinese herbal medicine (CHM) has good effects on treatment of MS and its animal model, experimental autoimmune encephalomyelitis (EAE) very well, so it is very important to understand the precise mechanism. Our previous study suggested that CD8+ autoreactive T cells in EAE had a lower encephalitogenic function but were unique and independent on pathogenic of EAE rather than their CD4+ counterparts. The aims of current study were to determine the pathological interrelationship between CD4+ and CD8+ autoreactive T cells in MS/EAE upon the HQGZWW treatment.Methods: Female C57BL/6 mice (n=8, each group) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide, and meantimely were treated with distilled water, prednisone, high dose or low dose HQGZWW. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4+ and CD8+ T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-g), interleukin (IL)-4 and IL-10 secretion of supernatant of cultured CD4+ and CD8+ T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG35-55 -specific CD8+ or CD4+ T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.Results: For aEAE, there were significant improvement of EAE score in both HQGZWW high dose and prednisone groups by EAE score and pathological examination of spinal cord. CD8+ CD3+ and CD4+CD3+ cells were around 90% pure of total CD3+ cells after CD8/CD4 bead enrichment in 4 groups, respectively. These cells were stimulated by MOG35–55 peptide and applied to proliferation assays. There is lower antigen-specific responses of CD8+ as well as CD4+ T cells in HQGZWW high dose and prednisone group, compared with HQGZWW low dose and distilled water groups. For cytokine profiles, the CD4+ and CD8+ T cell supernatants contained lower levels of IFN-g and higher levels of IL-4 and IL-10 in HQGZWW high dose and prednisone groups compared with HQGZWW low dose and distilled water groups. Finally, HQGZWW had similar effect at high dose level to typical conventional medicine prednisone on tEAE, but no effect at low dose level.Conclusion: Our data suggested that HQGZWW had similar effect at high dose level to typical conventional medicine prednisone on EAE, but no effect at low dose level, and it suggested that the protection role of HQGZWW on EAE might be upon Th2 cytokine secretion profile by either MOG35–55 specific CD8+ or CD4+ T cells.

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Experimental Autoimmune Encephalomyelitis Inhibited by Huangqi Guizhi Wuwu Decoction via Th2 Cytokine Enhancement

Peng

Zhu

Deng

et al. 2021

World Journal of Traditional Chinese Medicine

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Background: Huangqi Guizhi Wuwu decoction (HQGZWW) exhibits good effects when administered to treat multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Understanding the precise mechanism of this decoction is thus important. Based on the findings of our previous study, the aim of the present study was to understand the role of antigen-specific CD8+ T-cells on the pathogenesis of MS/EAE when HQGZWW is administered as treatment. Methods: Myelin oligodendrocyte glycoprotein (MOG) 35-55-induced mice were administered distilled water, prednisone, and high dose or low dose HQGZWW. After purified CD4+ and CD8+ T-cells were stimulated with the MOG35-55 peptide, proliferation and cytokine secretion assays were performed. To establish the adoptive transfer EAE model, naïve mice were injected with MOG35-55 - CD8+ or CD4+ T-cells. Results: Significant improvements in EAE score and pathology were observed in the high dose HQGZWW and prednisone groups. Compared to the low dose HQGZWW and distilled water groups, lower antigen-specific responses, lower levels of interferon-gamma, and higher levels of interleukin (IL)-4 and IL-10 from CD8+ and CD4+ T cells were observed in the high dose HQGZWW and prednisone groups. Finally, the EAE score was observed to be similar between the high dose HQGZWW group and prednisone group; however, this finding was not observed in the low dose HQGZWW group. Conclusion: Our findings suggest that high dose HQGZWW has similar effects on cell proliferation, cytokine secretion, and EAE score to prednisone, while low dose HQGZWW does not have such effect. The protective role of HQGZWW against EAE might thus depend on the Th2 cytokine secretion profile induced by either MOG35-55 specific CD8+ or CD4+ T-cells.

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Efficacy of Synthetic Peptide Corresponding to the ACTH-Like Sequence of Human Immunoglobulin G1 in Experimental Autoimmune Encephalomyelitis

Cited by 3 publications

References 26 publications

Characterization of myelin oligodendrocyte glycoprotein (MOG)35–55-specific CD8+ T cells in experimental autoimmune encephalomyelitis

Characterization of myelin oligodendrocyte glycoprotein (MOG)35–55-specific CD8+ T cells in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis inhibited by Huangqi Guizhi Wuwu Decoction by enhancing Th2 cytokine

Experimental Autoimmune Encephalomyelitis Inhibited by Huangqi Guizhi Wuwu Decoction via Th2 Cytokine Enhancement

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