Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells

Abstract

The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8+ T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8+ T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8+ T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3+ memory CD8+ T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.

Innate and adaptive T cells in influenza disease

“…Studies in guinea pigs also demonstrated that priming with the 2009 pandemic H1N1 virus confers protection against the 2013 avian H7N9 IAV [62]. Recently influenzaspecific tissue-resident memory (TRM) CD8 + T cells in the upper respiratory tract of mice were shown to be important in mediating protection from pulmonary influenza virus infection [63].…”

“…The presence of protective CD8 + TRM populations in the nasal tissue implies that these cytotoxic effectors are in place to contribute to the early control of infection. Indeed, in mouse studies the establishment of CD8 + TRM cells in the upper respiratory tract reduced viral replication in the nose as early as day 3 and day 5 after intranasal challenge, in a CD8 + T celldependent manner [63].…”

Tissue-Specific Control of Tissue-Resident Memory T Cells

“…73,85,86 Virus-specific CD69 + and CD69 + CD103 + CD8 + T cells carrying common T RM signature genes can be readily isolated from upper respiratory tract including nasal tissue and nasal-associated lymphoid tissues in mouse and tonsils in human. Distinct from TGF-β- and cognate antigen-dependent induction of lung T RM cells, both TGF-β and cognate antigen recognition are dispensable for upper respiratory tract T RM cells.…”

Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

“…The CXCR3 family chemokine CXCL10 is an IFNα/β signature gene, upregulated in patients with SLE . The CXCR3 chemokines CXCL9 and CXCL10 promote cell recruitment to sites of inflammation . During viral infection, DC‐derived CXCL10‐CXCR3 interactions can optimize both T‐ and B‐cell responses .…”