CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology

Kritika Mittal; Ekaterina Eremenko; Omer Berner; Yehezqel Elyahu; Itai Strominger; Daniella Apelblat; Anna Nemirovsky; Ivo Spiegel; Alon Monsonego

doi:10.1016/j.isci.2019.05.039

CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology

iScience. 2019 Jun 28:16:298-311. doi: 10.1016/j.isci.2019.05.039. Epub 2019 May 30.

Authors

Kritika Mittal¹, Ekaterina Eremenko¹, Omer Berner¹, Yehezqel Elyahu¹, Itai Strominger¹, Daniella Apelblat², Anna Nemirovsky¹, Ivo Spiegel², Alon Monsonego³

Affiliations

¹ The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
² Department of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.
³ The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Zlotowski Center for Neuroscience, The National Institute of Biotechnology in the Negev, Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. Electronic address: alonmon@bgu.ac.il.

Abstract

Microglia play a key role in innate immunity in Alzheimer disease (AD), but their role as antigen-presenting cells is as yet unclear. Here we found that amyloid β peptide (Aβ)-specific T helper 1 (Aβ-Th1 cells) T cells polarized to secrete interferon-γ and intracerebroventricularly (ICV) injected to the 5XFAD mouse model of AD induced the differentiation of major histocompatibility complex class II (MHCII)+ microglia with distinct morphology and enhanced plaque clearance capacity than MHCII- microglia. Notably, 5XFAD mice lacking MHCII exhibited an enhanced amyloid pathology in the brain along with exacerbated innate inflammation and reduced phagocytic capacity. Using a bone marrow chimera mouse model, we showed that infiltrating macrophages did not differentiate to MHCII+ cells following ICV injection of Aβ-Th1 cells and did not support T cell-mediated amyloid clearance. Overall, we demonstrate that CD4 T cells induce a P2ry12+ MHCII+ subset of microglia, which play a key role in T cell-mediated effector functions that abrogate AD-like pathology.

Keywords: Biological Sciences; Cell Biology; Immunology; Neuroscience.