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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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Frequency of cytokine producing cells in Tm subsets. Intracellular staining for cytokines was assessed for CD4+, CD45RO+ T cells that were immediately stimulated after isolation as described in Fig. 1; 104 cells were collected for each analysis of normal blood (n = 11), RAPB (n = 9), RASF (n = 8), and RAST (n = 4). The total number of cytokine-producing cells detected in each sample is shown in the upper right corner of each graph. The frequency of each subset of cytokine-producing cells is shown (mean ± standard error of the mean). The frequency was derived by using the total number of cytokine-producing cells as the denominator (× 100). Statistically significant differences are described in Results.
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Figure 2: Frequency of cytokine producing cells in Tm subsets. Intracellular staining for cytokines was assessed for CD4+, CD45RO+ T cells that were immediately stimulated after isolation as described in Fig. 1; 104 cells were collected for each analysis of normal blood (n = 11), RAPB (n = 9), RASF (n = 8), and RAST (n = 4). The total number of cytokine-producing cells detected in each sample is shown in the upper right corner of each graph. The frequency of each subset of cytokine-producing cells is shown (mean ± standard error of the mean). The frequency was derived by using the total number of cytokine-producing cells as the denominator (× 100). Statistically significant differences are described in Results.

Mentions: A compilation of the frequency of cells that produced each cytokine from a number of donors is shown in Fig. 2. After a brief in vitro stimulation, the majority of Tm obtained from normal donors (n = 11) produced IL-2 alone (75 ± 4%; mean ± SEM). Fewer cells produced the combination of IL-2 and IFN-γ (14 ± 3%). Relatively infrequent cells expressed a highly polarized phenotype by producing either IFN-γ (6 ± 1%) or IL-4 alone (4 ± 1%). Less than 1% of the cells produced the combination of IFN-γ and 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)

Frequency of cytokine producing cells in Tm subsets. Intracellular staining for cytokines was assessed for CD4+, CD45RO+ T cells that were immediately stimulated after isolation as described in Fig. 1; 104 cells were collected for each analysis of normal blood (n = 11), RAPB (n = 9), RASF (n = 8), and RAST (n = 4). The total number of cytokine-producing cells detected in each sample is shown in the upper right corner of each graph. The frequency of each subset of cytokine-producing cells is shown (mean ± standard error of the mean). The frequency was derived by using the total number of cytokine-producing cells as the denominator (× 100). Statistically significant differences are described in Results.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC17825&req=5

Figure 2: Frequency of cytokine producing cells in Tm subsets. Intracellular staining for cytokines was assessed for CD4+, CD45RO+ T cells that were immediately stimulated after isolation as described in Fig. 1; 104 cells were collected for each analysis of normal blood (n = 11), RAPB (n = 9), RASF (n = 8), and RAST (n = 4). The total number of cytokine-producing cells detected in each sample is shown in the upper right corner of each graph. The frequency of each subset of cytokine-producing cells is shown (mean ± standard error of the mean). The frequency was derived by using the total number of cytokine-producing cells as the denominator (× 100). Statistically significant differences are described in Results.
Mentions: A compilation of the frequency of cells that produced each cytokine from a number of donors is shown in Fig. 2. After a brief in vitro stimulation, the majority of Tm obtained from normal donors (n = 11) produced IL-2 alone (75 ± 4%; mean ± SEM). Fewer cells produced the combination of IL-2 and IFN-γ (14 ± 3%). Relatively infrequent cells expressed a highly polarized phenotype by producing either IFN-γ (6 ± 1%) or IL-4 alone (4 ± 1%). Less than 1% of the cells produced the combination of IFN-γ and 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