Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4

作者： Sharon A. Sagan*1,2, Andrés Cruz-Herranz*1, Collin M. Spencer1,2, Peggy P. Ho3, Lawrence Steinman3, Ari J. Green1, Raymond A. Sobel4, Scott S. Zamvil1,2 1Department of Neurology,University of California, 2Program in Immunology,University of California, 3Department of Neurology and Neurological Sciences,Stanford University, 4Department of Pathology,Stanford University

简介：

Overview

This protocol outlines the induction of paralysis and opticospinal inflammation through the transfer of aquaporin-4 (AQP4)-specific T cells from AQP4 -/- mice into wild-type (WT) mice. Additionally, it describes the use of serial optical coherence tomography to monitor visual system dysfunction.

Key Study Components

Area of Science

• Neuroscience
• Immunology
• Optical Imaging

Background

• Aquaporin-4 (AQP4) is implicated in CNS autoimmune diseases.
• Understanding T cell responses can provide insights into neuromyelitis optica.
• Optical coherence tomography allows for noninvasive monitoring of retinal health.
• This study aims to elucidate the role of AQP4-specific T cells in inflammatory visual disorders.

Purpose of Study

• To induce CNS autoimmune disease via adoptive T cell transfer.
• To monitor the effects on the CNS and visual system.
• To investigate the pathogenic role of AQP4-specific T cells.

Methods Used

• Adoptive transfer of AQP4-specific T cells from AQP4 -/- mice.
• Subcutaneous immunization with AQP4 peptides.
• Optical coherence tomography for in vivo retinal imaging.
• Flow cytometric analysis of T cell responses.

Main Results

• Strong proliferative T cell responses observed in AQP4 knockout mice.
• Unique TCR repertoires identified in AQP4-specific T cells.
• Effective monitoring of retinal injury using optical coherence tomography.
• Pathogenic T cell responses are regulated by thymic negative selection.

Conclusions

• The protocol successfully induces CNS autoimmune disease.
• Optical coherence tomography is a valuable tool for monitoring retinal health.
• AQP4-specific T cells play a significant role in visual disorders.

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