Saunderson et al. explored the in vivo cellular and molecular requirements under which exosomes derived from antigen-exposed B cells present antigens and induce a cytotoxic CD8+ T lymphocyte response. They identified CD4+ T cells and, unexpectedly, NK cells, but not B cells, as crucial helper cells, and host MHC I molecules and splenic langerin+CD8α+ dendritic cells (DCs) as critical for antigen cross-presentation.

Exosomes are lipid nanovesicles released after fusion of the endosomal limiting membrane with the plasma membrane. In this study, we investigated the requirement for CD4 T cells, B cells, and NK cells to provide help for CD8 T cell-mediated response to B cell-derived exosomes. CTL responses to Ag-loaded exosomes were dependent on host MHC class I, with a critical role for splenic langerin+ CD8alpha+ dendritic cells (DCs) in exosomal Ag cross-presentation. In addition, there was an absolute dependence on the presence of CD4 T cells, CD8 T cells, and NK cells, where the loss of any one of these subsets led to a complete loss of CTL response. Interestingly, NK cell depletion experiments demonstrated a critical cutoff point for depletion efficacy, with low-level residual NK cells providing sufficient help to allow optimal CD8 T cell proliferative responses to exosomal protein. Despite the potential role for B cells in the response to B cell-derived exosomal proteins, B cell depletion did not alter the exosome-induced CTL response. Similarly, a possible role for the BCR or circulating Ab in mediating CTL responses to B cell-derived exosomes was ruled out using DHLMP2A mice, which lack secreted and membrane-bound Ab, yet harbor marginal zone and follicular B cells. In contrast, CTL responses to DC-derived exosomes were significantly inhibited within Ab-deficient DHLMP2A mice compared with wild-type mice. However, this response was not restored upon serum transfer, implicating a role for the BCR, but not circulating Ab, in DC-derived exosome responses.

Author Info: (1) Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand. (2) Department of Microbiology and Immunology, University of Otago, Dunedin 90

Author Info: (1) Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand. (2) Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand alex.mclellan@otago.ac.nz.