Human CD4+CD3- innate-like T cells provide a source of TNF and lymphotoxin-αβ and are elevated in rheumatoid arthritis

J Immunol. 2013 Nov 1;191(9):4611-8. doi: 10.4049/jimmunol.1301672. Epub 2013 Sep 27.

Abstract

Innate lymphoid cells encompass a diverse array of lymphocyte subsets with unique phenotype that initiate inflammation and provide host defenses in specific microenvironments. In this study, we identify a rare human CD4(+)CD3(-) innate-like lymphoid population with high TNF expression that is enriched in blood from patients with rheumatoid arthritis. These CD4(+)CD3(-) cells belong to the T cell lineage, but the lack of AgR at the cell surface renders them nonresponsive to TCR-directed stimuli. By developing a culture system that sustains survival, we show that CD4(+)CD3(-) innate-like T cells display IL-7-dependent induction of surface lymphotoxin-αβ, demonstrating their potential to modify tissue microenvironments. Furthermore, expression of CCR6 on the CD4(+)CD3(-) population defines a CD127(high) subset that is highly responsive to IL-7. This CD4(+)CD3(-) population is enriched in the peripheral blood from rheumatoid arthritis patients, suggesting a link to their involvement in chronic inflammatory disease.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • CD3 Complex / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Line
  • Female
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Humans
  • Inflammation
  • Interleukin-7 / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphotoxin alpha1, beta2 Heterotrimer / immunology
  • Lymphotoxin alpha1, beta2 Heterotrimer / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Receptors, CCR6 / metabolism
  • Tumor Necrosis Factors / metabolism*

Substances

  • CCR6 protein, human
  • CD3 Complex
  • Homeodomain Proteins
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • Lymphotoxin alpha1, beta2 Heterotrimer
  • Receptors, CCR6
  • Tumor Necrosis Factors
  • RAG-1 protein