B cells promote Alzheimers disease via cytolytic CD8+ T cells

National Institute On Aging

Investigators

Abstract

Compared to age/sex-matched B-cell sufficient littermates, 2xTgAD/BKO, 5xFAD/BKO and 3xTgAD/BKO mice exhibited reduced anxiety and improved memory deficits. 2xTgAD/BKO, 5xFAD/BKO and 3xTgAD/BKO mice contained significantly fewer A-beta plaques in the brain subiculum than their age- and sex-matched littermates. These data, which we recently reported (Kim et al., Nature Comm., 2021), indicate that AD manifestation requires B cells. However, recent report from others also implicates CD8+ T cells in AD. Because our B cells in aging acquire a superb ability to elicit antigen-specific CD8+ T cells, here we hypothesize that activated in AD hosts B cells induce the generation of CD8+ T cells that infiltrate into the brain, thereby cause harmful neurodegeneration in AD. To test this hypothesis, we quantified brain CD8+ T cells in three different murine models of AD, 5xFAD, APP/PS1, and 3xTgAD. In parable, we also transiently depleted circulating CD8+ T cells in 5xFAD mice by i.p. injecting anti-CD8a Ab. Our preliminary data indicate that 1, CD8+ T cells increased in the brain of AD mice; 2, Depletion of CD8+ T cells amelirates AD symptomes; and 3, B-cell deficiency also decrease the increased CD8+ T cells in the brain. These experiments are being repeated to confirm the importance of B cells in inductuion of brain-infiltrating CD8+ T cells. Overall, this project which we started a few months ago is progressing well.