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Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells.

Davis LS, Cush JJ, Schulze-Koops H, Lipsky PE - Arthritis Res. (2000)

Bottom Line: RAPB Tm contained significantly more IFN-gamma producers than normal cells.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT
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.

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Representative cytokine profiles of Tm isolated from healthy donors and RA patients. CD4+, CD45RO+ T cells were isolated from the blood and synovial fluid of an RA patient (RA Patient 1), the blood and synovial tissue of an RA patient (RA Patient 7), and the blood of a healthy donor (Normal 1). Intracellular cytokines were assessed for peripheral blood and synovial cells from RA patients or blood of healthy donors. Cells were briefly stimulated for 6 h, fixed, permeabilized and stained with directly labeled control antibodies or anti-IFN-γ-FITC in combination with either PE-labeled anti-IL-2 or PE-labeled anti-IL-4, as indicated on the axes; 104 cells were collected for each analysis. The numbers shown represent the percentages of cells in each quadrant. Control staining with IgG-PE and IgG-FITC was carried out for each sample as shown (Normal 1) and the background was subtracted. Samples were obtained from matching RA blood and synovial fluid (n = 5), matching blood and synovial tissue (n = 3), and normal blood (n = 11). Statistical analysis of all samples evaluated for intracellular cytokines immediately after isolation is shown in Fig. 2.
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Figure 1: Representative cytokine profiles of Tm isolated from healthy donors and RA patients. CD4+, CD45RO+ T cells were isolated from the blood and synovial fluid of an RA patient (RA Patient 1), the blood and synovial tissue of an RA patient (RA Patient 7), and the blood of a healthy donor (Normal 1). Intracellular cytokines were assessed for peripheral blood and synovial cells from RA patients or blood of healthy donors. Cells were briefly stimulated for 6 h, fixed, permeabilized and stained with directly labeled control antibodies or anti-IFN-γ-FITC in combination with either PE-labeled anti-IL-2 or PE-labeled anti-IL-4, as indicated on the axes; 104 cells were collected for each analysis. The numbers shown represent the percentages of cells in each quadrant. Control staining with IgG-PE and IgG-FITC was carried out for each sample as shown (Normal 1) and the background was subtracted. Samples were obtained from matching RA blood and synovial fluid (n = 5), matching blood and synovial tissue (n = 3), and normal blood (n = 11). Statistical analysis of all samples evaluated for intracellular cytokines immediately after isolation is shown in Fig. 2.

Mentions: Initial experiments delineated cytokine production by freshly isolated CD4+ CD45RO+ T cells obtained from matching samples of RAPB and RASF. A representative sample is shown in Fig. 1 (RA patient1). The majority of peripheral blood T cells from RA patients secreted IL-2 alone, whereas fewer cells secreted IFN-γ alone or in combination with IL-2. By contrast, the CD4+ T cells isolated from the synovial fluid demonstrated a significant increase in the percentage of cells that produced IFN-γ alone or in combination with IL-2, whereas a decrease was observed in the percentage of cells that secreted IL-2 alone. Few cells from peripheral blood or synovial fluid produced IL-4.


Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells.

Davis LS, Cush JJ, Schulze-Koops H, Lipsky PE - Arthritis Res. (2000)

Representative cytokine profiles of Tm isolated from healthy donors and RA patients. CD4+, CD45RO+ T cells were isolated from the blood and synovial fluid of an RA patient (RA Patient 1), the blood and synovial tissue of an RA patient (RA Patient 7), and the blood of a healthy donor (Normal 1). Intracellular cytokines were assessed for peripheral blood and synovial cells from RA patients or blood of healthy donors. Cells were briefly stimulated for 6 h, fixed, permeabilized and stained with directly labeled control antibodies or anti-IFN-γ-FITC in combination with either PE-labeled anti-IL-2 or PE-labeled anti-IL-4, as indicated on the axes; 104 cells were collected for each analysis. The numbers shown represent the percentages of cells in each quadrant. Control staining with IgG-PE and IgG-FITC was carried out for each sample as shown (Normal 1) and the background was subtracted. Samples were obtained from matching RA blood and synovial fluid (n = 5), matching blood and synovial tissue (n = 3), and normal blood (n = 11). Statistical analysis of all samples evaluated for intracellular cytokines immediately after isolation is shown in Fig. 2.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC17825&req=5

Figure 1: Representative cytokine profiles of Tm isolated from healthy donors and RA patients. CD4+, CD45RO+ T cells were isolated from the blood and synovial fluid of an RA patient (RA Patient 1), the blood and synovial tissue of an RA patient (RA Patient 7), and the blood of a healthy donor (Normal 1). Intracellular cytokines were assessed for peripheral blood and synovial cells from RA patients or blood of healthy donors. Cells were briefly stimulated for 6 h, fixed, permeabilized and stained with directly labeled control antibodies or anti-IFN-γ-FITC in combination with either PE-labeled anti-IL-2 or PE-labeled anti-IL-4, as indicated on the axes; 104 cells were collected for each analysis. The numbers shown represent the percentages of cells in each quadrant. Control staining with IgG-PE and IgG-FITC was carried out for each sample as shown (Normal 1) and the background was subtracted. Samples were obtained from matching RA blood and synovial fluid (n = 5), matching blood and synovial tissue (n = 3), and normal blood (n = 11). Statistical analysis of all samples evaluated for intracellular cytokines immediately after isolation is shown in Fig. 2.
Mentions: Initial experiments delineated cytokine production by freshly isolated CD4+ CD45RO+ T cells obtained from matching samples of RAPB and RASF. A representative sample is shown in Fig. 1 (RA patient1). The majority of peripheral blood T cells from RA patients secreted IL-2 alone, whereas fewer cells secreted IFN-γ alone or in combination with IL-2. By contrast, the CD4+ T cells isolated from the synovial fluid demonstrated a significant increase in the percentage of cells that produced IFN-γ alone or in combination with IL-2, whereas a decrease was observed in the percentage of cells that secreted IL-2 alone. Few cells from peripheral blood or synovial fluid produced IL-4.

Bottom Line: RAPB Tm contained significantly more IFN-gamma producers than normal cells.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus