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

Timona S. Tyllis, Kevin A. Fenix, Todd S. Norton, Ervin E. Kara, Duncan R. McKenzie, Shannon C. David, Mohammed Alsharifi, Di Yu, Shaun R. McColl, Iain Comerford

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11 Citations (Scopus)


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.

Original languageEnglish
Article number626199
JournalFrontiers in Immunology
Publication statusPublished or Issued - 13 Jul 2021
Externally publishedYes


  • CXCR5CD8 T cells
  • antibody response
  • class switching
  • immunization
  • infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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