Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells.
CD4+ memory T cells (Tm) from rheumatoid arthritis peripheral blood (RAPB) or peripheral blood from normal donors produced IL-2, whereas fewer cells secreted IFN-gamma or IL-4 after a brief stimulation. RAPB Tm contained significantly more IFN-gamma producers than normal cells. Many rheumatoid arthritis (RA) synovial Tm produced IFN-gamma alone (40%) and fewer cells produced IL-2 or IL-4. An in vitro model was employed to generate polarized T-helper (Th) effectors. Normal and RAPB Tm differentiated into both IFN-gamma- and IL-4-producing effectors. RA synovial fluid (RASF) Tm demonstrated defective responsiveness, exhibiting diminished differentiation of IL-4 effectors, whereas RA synovial tissue (RAST) Tm exhibited defective generation of IFN-gamma and IL-4 producers.
Davis
L S
LS
The Harold C Simmons Arthritis Research Center and Rheumatic Diseases Division, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8884, USA. laurie.davis@UTSouthwestern.edu
Cush
J J
JJ
Schulze-Koops
H
H
Lipsky
P E
PE
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D007106:Immune Sera; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens