CXCR5 + CD8 + T Cells Shape Antibody Responses In Vivo Following Protein Immunisation and Peripheral Viral Infection.

Crosstalk between T and B cells is crucial for generating high-affinity, class-switched antibody responses. The roles of CD4 ⁺ T cells in this process have been well-characterised. In contrast, regulation of antibody responses by CD8 ⁺ T cells is significantly less defined. CD8 ⁺ T cells are principally recognised for eliciting cytotoxic responses in peripheral tissues and forming protective memory. However, recent findings have identified a novel population of effector CD8 ⁺ T cells that co-opt a differentiation program characteristic of CD4 ⁺ T follicular helper (Tfh) cells, upregulate the chemokine receptor CXCR5 and localise to B cell follicles. While it has been shown that CXCR5 ⁺ CD8 ⁺ T cells mediate the removal of viral reservoirs in the context of follicular-trophic viral infections and maintain the response to chronic insults by virtue of progenitor/stem-like properties, it is not known if CXCR5 ⁺ CD8 ⁺ T cells arise during acute peripheral challenges in the absence of follicular infection and whether they influence B cell responses in vivo in these settings. Using the ovalbumin-specific T cell receptor transgenic (OT-I) system in an adoptive transfer-immunisation/infection model, this study demonstrates that CXCR5 ⁺ CD8 ⁺ T cells arise in response to protein immunisation and peripheral viral infection, displaying a follicular-homing phenotype, expression of cell surface molecules associated with Tfh cells and limited cytotoxic potential. Furthermore, studies assessing the B cell response in the presence of OT-I or Cxcr5 ^-/- OT-I cells revealed that CXCR5 ⁺ CD8 ⁺ T cells shape the antibody response to protein immunisation and peripheral viral infection, promoting class switching to IgG2c in responding B cells. Overall, the results highlight a novel contribution of CD8 ⁺ T cells to antibody responses, expanding the functionality of the adaptive immune system.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Tyllis, Fenix, Norton, Kara, McKenzie, David, Alsharifi, Yu, McColl and Comerford.)