Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus
TGF-beta has marked inhibitory effects on the immune system but also serves as a costimulatory factor in the development of T cells with down-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2...
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| Veröffentlicht in: | The Journal of immunology (1950) 1998-03, Vol.160 (5), p.2539-2545 |
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| creator | Ohtsuka, K Gray, J D Stimmler, M M Toro, B Horwitz, D A |
| description | TGF-beta has marked inhibitory effects on the immune system but also serves as a costimulatory factor in the development of T cells with down-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source. The objective of this study was to compare levels of constitutive, anti-CD2-induced and cytokine-regulated TGF-beta produced by blood lymphocytes from patients with systemic lupus erythematosus (SLE) in comparison with healthy controls. Using a highly sensitive and specific bioassay to assess TGF-beta, we report that unstimulated PBL from SLE patients, especially the NK cell subset, produced decreased levels of active TGF-beta. In response to anti-CD2, concentrations of active and total TGF-beta were also decreased in SLE. After learning that IL-2 and TNF-alpha enhance lymphocyte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrations. Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity. |
| doi_str_mv | 10.4049/jimmunol.160.5.2539 |
| format | Article |
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This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source. The objective of this study was to compare levels of constitutive, anti-CD2-induced and cytokine-regulated TGF-beta produced by blood lymphocytes from patients with systemic lupus erythematosus (SLE) in comparison with healthy controls. Using a highly sensitive and specific bioassay to assess TGF-beta, we report that unstimulated PBL from SLE patients, especially the NK cell subset, produced decreased levels of active TGF-beta. In response to anti-CD2, concentrations of active and total TGF-beta were also decreased in SLE. After learning that IL-2 and TNF-alpha enhance lymphocyte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrations. Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. 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Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity.</description><subject>Adult</subject><subject>Aged</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>Cells, Cultured</subject><subject>Down-Regulation - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G - biosynthesis</subject><subject>Interleukin-10 - pharmacology</subject><subject>Interleukin-2 - pharmacology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Lupus Erythematosus, Systemic - immunology</subject><subject>Lupus Erythematosus, Systemic - metabolism</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Transforming Growth Factor beta - antagonists & inhibitors</subject><subject>Transforming Growth Factor beta - biosynthesis</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAURoMoOj5-gQhZuet4kzRpsxTfILjRdUjTG6bSTGqTIv33Vhzdurqbcz64h5BzBusSSn313oUwbWO_ZgrWcs2l0HtkxaSEQilQ-2QFwHnBKlUdkeOU3gFAAS8PyaEudV0DrIi5RTeiTdjSYYzt5HIXtzR6-vpwXzSYLW1m2s9h2EQ3Z0zUjzHQweYOtznRzy5vaJpTxtA52k_DlCiOc95gsDmmKZ2SA2_7hGe7e0Le7u9ebx6L55eHp5vr58KJSuWi5rZ1DIXVtcLWNlI2Qta8AYWNBl170VqvUaOt1WIAaF9rrRVzXlZaeHFCLn92ly8-JkzZhC457Hu7xTglU-mKl4yLf0GmeCVKVS2g-AHdGFMa0Zth7IIdZ8PAfPc3v_0XB4w03_0X62I3PzUB2z9nF1x8AUHchZk</recordid><startdate>19980301</startdate><enddate>19980301</enddate><creator>Ohtsuka, K</creator><creator>Gray, J D</creator><creator>Stimmler, M M</creator><creator>Toro, B</creator><creator>Horwitz, D A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19980301</creationdate><title>Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus</title><author>Ohtsuka, K ; 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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged B-Lymphocytes - immunology B-Lymphocytes - metabolism Cells, Cultured Down-Regulation - immunology Female Humans Immunoglobulin G - biosynthesis Interleukin-10 - pharmacology Interleukin-2 - pharmacology Killer Cells, Natural - metabolism Lupus Erythematosus, Systemic - immunology Lupus Erythematosus, Systemic - metabolism Lymphocytes - immunology Lymphocytes - metabolism Male Middle Aged Transforming Growth Factor beta - antagonists & inhibitors Transforming Growth Factor beta - biosynthesis Transforming Growth Factor beta - pharmacology |
| title | Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus |
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