Clonally related CD8+ T cells responsible for rapid population of both diffuse nasal-associated lymphoid tissue and lung after respiratory virus infection

J Immunol. 2011 Jul 15;187(2):835-41. doi: 10.4049/jimmunol.1100125. Epub 2011 Jun 20.

Abstract

The immune system has evolved to use sophisticated mechanisms to recruit lymphocytes to sites of pathogen exposure. Trafficking pathways are precise. For example, lymphocytes that are primed by gut pathogens can, in some cases, be imprinted with CCR9 membrane receptors, which can influence migration to the small intestine. Currently, little is known about T cell trafficking to the upper respiratory tract or the relationship between effectors that migrate to the diffuse nasal-associated lymphoid tissue (d-NALT), the lower airways, and the lung. To determine whether a T cell primed by Ag from a respiratory pathogen is imprinted for exclusive trafficking to the upper or lower respiratory tract or whether descendents from that cell have the capacity to migrate to both sites, we inoculated mice by the intranasal route with Sendai virus and conducted single-cell-sequencing analyses of CD8(+) T lymphocytes responsive to a K(b)-restricted immunodominant peptide, FAPGNYPAL (Tet(+)). Cells from the d-NALT, lung airways (bronchoalveolar lavage), lung, and mediastinal lymph node were examined 10 d postinfection to determine TCR usage and clonal relationships. We discovered that 1) Tet(+) cells were heterogeneous but preferentially used TCR elements TRAV6, TRAV16, and TRBD1; 2) both N and C termini of Vα and Vβ TCR junctions frequently encompassed charged residues, perhaps facilitating TCR αβ pairing and interactions with a neutral target peptide; and 3) T cells in the d-NALT were often clonally related to cells in the lower respiratory tract.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Movement / immunology*
  • Clone Cells
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • H-2 Antigens / administration & dosage
  • H-2 Antigens / immunology
  • H-2 Antigens / metabolism
  • Immunodominant Epitopes / metabolism
  • Immunoglobulin Variable Region / metabolism
  • Lung / immunology*
  • Lung / pathology
  • Lung / virology
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / pathology
  • Lymphoid Tissue / virology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / pathology
  • Nasal Mucosa / virology
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / pathology
  • Respiratory Tract Infections / virology
  • Respirovirus Infections / immunology*
  • Respirovirus Infections / pathology
  • Respirovirus Infections / virology
  • Sendai virus / immunology*
  • Sendai virus / isolation & purification

Substances

  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Immunodominant Epitopes
  • Immunoglobulin Variable Region
  • Receptors, Antigen, T-Cell, alpha-beta