In:
Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 1 ( 2018-01), p. e419-
Abstract:
To characterize the brain-infiltrating immune cell repertoire in Rasmussen encephalitis (RE) with special focus on the subsets, clonality, and their cytokine profile. Methods: The immune cell infiltrate of freshly isolated brain tissue from RE was phenotypically and functionally characterized using immunohistology, flow cytometry, and T-cell receptor (TCR) deep sequencing. Identification of clonally expanded T-cell clones (TCCs) was achieved by combining flow cytometry sorting of CD4 + and CD8 + T cells and high-throughput TCR Vβ-chain sequencing. The most abundant brain-infiltrating TCCs were isolated and functionally characterized. Results: We found that CD4 + , CD8 + , and also γδ T cells infiltrate the brain tissue in RE. Further analysis surprisingly revealed that not only brain-infiltrating CD8 + but also CD4 + T cells are clonally expanded in RE. All 3 subsets exhibited a Tc1/Th1 phenotype characterized by the production of interferon (IFN)-γ and TNF. Broad cytokine profiling at the clonal level showed strong production of IFN-γ and TNF and also secretion of interleukin (IL)-5, IL-13, and granzyme B, both in CD4 + and CD8 + T cells. Conclusions: CD8 + T cells were until now considered the central players in the immunopathogenesis of RE. Our study adds to previous findings and highlights that CD4 + TCCs and γδ T cells that secrete IFN-γ and TNF are also involved. These findings underline the complexity of T-cell immunity in RE and suggest a specific role for CD4 + T cells in orchestrating the CD8 + T-cell effector immune response.
Type of Medium:
Online Resource
ISSN:
2332-7812
DOI:
10.1212/NXI.0000000000000419
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
2767740-0
