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

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.

• Authors: Vasileios Bekiaris, John R Šedy, Maura Rossetti, Roberto Spreafico, Shilpi Sharma, Antje Rhode-Kurnow, Brian C Ware, Nini Huang, Matthew G Macauley, Paula S Norris, Salvatore Albani, Carl F Ware
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 191 Issue 9 Pg. 4611-8 (Nov 01 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 24078690 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Adult
• Aged
• Animals
• Arthritis, Rheumatoid (immunology, metabolism)
• CD3 Complex (metabolism)
• CD4-Positive T-Lymphocytes (immunology, 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, metabolism)
• Male
• Mice
• Mice, Knockout
• Middle Aged
• Receptors, CCR6 (metabolism)
• Tumor Necrosis Factors (metabolism)