Dataset Information

CD4⁺ T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

ABSTRACT: Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell-mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4⁺ T-cell infiltration into the retina. Adoptive transfer of CD4⁺ T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-γ-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.

SUBMITTER: Khanh Vu TH

PROVIDER: S-EPMC7397460 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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CD4<sup>+</sup> T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

Khanh Vu Thi Hong TH Chen Huihui H Pan Li L Cho Kin-Sang KS Doesburg Djoeke D Thee Eric F EF Wu Nan N Arlotti Elisa E Jager Martine J MJ Chen Dong Feng DF

The American journal of pathology 20200508 8

Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell-mediated responses, is thought to be intricately involved, but the exact roles remain elusiv ...[more]

PMID: 32389572

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Project description:BackgroundRespiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.MethodsWe focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models.ResultsFor each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.ConclusionIn conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

Dataset Information

CD4⁺ T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

Publications

CD4<sup>+</sup> T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

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Dataset Information

CD4+ T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

Publications

CD4<sup>+</sup> T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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CD4⁺ T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy.