CD4+ T cell persistence and function after infection are maintained by low-level peptide:MHC class II presentation

J Immunol. 2013 Mar 15;190(6):2828-34. doi: 10.4049/jimmunol.1202183. Epub 2013 Feb 4.

Abstract

CD4(+) memory-phenotype T cells decline over time when generated in response to acute infections cleared by other components of the immune system. Therefore, it was of interest to assess the stability of CD4(+) T cells during a persistent Salmonella infection, which is typical of persistent phagocytic infections that are controlled by this lymphocyte subset. We found that CD4(+) T cells specific for Salmonella peptide:MHC class II (MHCII) ligands were numerically stable for >1 y after initial oral infection. This stability was associated with peptide:MHCII-driven proliferation by a small number of T cells in the secondary lymphoid organs that harbored bacteria. The persistent population consisted of multifunctional Th1 cells that induced PD-1 and became exhausted when transferred to hosts expressing the specific peptide:MHCII ligand in all parts of the body. Thus, persistent infection of phagocytes produced a CD4(+) T cell population that was stably maintained by low-level peptide:MHCII presentation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / microbiology*
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Immunophenotyping / methods
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Salmonella Infections / immunology*
  • Salmonella Infections / metabolism
  • Salmonella Infections / pathology
  • Salmonella typhi / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • I-A(b) antigen, mouse
  • Peptide Fragments