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

Proc Natl Acad Sci U S A. 2017 May 16;114(20):5225-5230. doi: 10.1073/pnas.1620194114. Epub 2017 May 1.

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.

Keywords: CD8 T-cell priming; influenza virus; nasal-associated lymphoid tissue; respiratory tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Immunity, Mucosal / immunology*
  • Immunization
  • Influenza A virus / immunology
  • Influenza Vaccines / immunology
  • Lymph Nodes / physiology
  • Lymphoid Tissue / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / physiology
  • Orthomyxoviridae Infections / immunology
  • Respiratory Tract Infections
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccination

Substances

  • Influenza Vaccines