Human CD4+CD3- innate-like T cells provide a source of TNF and lymphotoxin-αβ and are elevated in rheumatoid arthritis.
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.
Infectious and Inflammatory Disease Center, Sanford|Burnham Medical Research Institute, La Jolla, CA 92037.
Vasileios
V
Bekiaris
John R
JR
Šedy
Maura
M
Rossetti
Roberto
R
Spreafico
Shilpi
S
Sharma
Antje
A
Rhode-Kurnow
Brian C
BC
Ware
Nini
N
Huang
Matthew G
MG
Macauley
Paula S
PS
Norris
Salvatore
S
Albani
Carl F
CF
Ware
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007249:Inflammation; D015851:Interleukin-7 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism*
C106311:CCR6 protein, human; D017252:CD3 Complex; D018398:Homeodomain Proteins; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D054399:Receptors, CCR6; D048069:Tumor Necrosis Factors; C064658:RAG-1 protein