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. 2020 Sep 22;21(18):6966. doi: 10.3390/ijms21186966

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Proposed model of CD4 T cell-derived IL-21 help to CD8 T cells in the brain during PyV-infection. (A) CD4 T cells with a high density of high-affinity TCRs are CXCR5^hiPD-1^hi and produce IL-21 that is received by the CD8 T cells in the brain. This is likely occurring around 15 dpi. (B) IL-21 binds to the IL21R on CD8 T cells and starts a signaling cascade that helps guide their differentiation into bT_RM, metabolically, phenotypically, and functionally. ETC, electron transport chain. Figure image created with BioRender.com.