Exogenous interleukin-2 does not reverse the immunoinhibitory effects of 1,25-dihydroxyvitamin D3 on human peripheral blood lymphocyte immunoglobulin production
Autor: | Stanley C. Jordan, John S. Adams, Mieko Toyoda, Rebecca Sakai, Jacques M. Lemire |
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Rok vydání: | 1990 |
Předmět: |
CD4-Positive T-Lymphocytes
Interleukin 2 medicine.medical_treatment Lymphocyte Immunology Immunoglobulins Biology Lymphocyte Activation T-Lymphocytes Regulatory Peripheral blood mononuclear cell Calcitriol medicine Humans Lymphocytes Receptor Molecular Biology Cells Cultured B-Lymphocytes Cell growth Molecular biology Recombinant Proteins Cytokine medicine.anatomical_structure Cell culture Interleukin-2 Immunosuppressive Agents CD8 medicine.drug |
Zdroj: | Molecular Immunology. 27:95-100 |
ISSN: | 0161-5890 |
DOI: | 10.1016/0161-5890(90)90064-7 |
Popis: | 1,25-Dihydroxyvitamin D 3 (1,25-D 3 ) is known to have potent inhibitory effects on human peripheral blood mononuclear cell (PBMC) functions. Previous experiments suggest that addition of interleukin-2 (IL-2) to cell cultures can reverse the antiproliferative action of 1,25-D 3 . Previous studies have also shown that the CD4 + T-cell subset is more sensitive to the antiproliferative actions of 1,25-D 3 than are the CD8 + T-cells. The objective of this study was to determine whether exogenous IL-2 could reverse the antiproliferative and immunoinhibitory action (inhibition of Ig production) in mitogen-activated PBMC cultures and in fluorescein-activated cell sorting (FACS) experiments where CD8 + T-cells were removed from PBMCs before mitogen stimulation with/without exogenous IL-2 added. In these studies, addition of IL-2 to mitogen-activated, 1,25-D 3 -treated PBMCs allowed the cells to overcome the 1,25-D 3 suppressive effect on cell proliferation. However, exogenous IL-2 did not overcome the 1,25-D 3 -mediated inhibitory effect on PBMC Ig production. Using FACS lymphocyte populations (CD4 + , CD8 + and B-cells), we showed that CD4 + T-cell-directed Ig synthesis in co-culture with autologous B-cells was inhibitable by incubation of cells with 1,25-D 3 , but Ig synthesis was restored to near-normal levels by addition of exogenous IL-2. This clearly contrasts with the inability of IL-2 to reverse the 1,25-D 3 inhibitory effect on Ig synthesis in PBMCs. In other experiments, when CD8 + cells were removed from mitogen-stimulated, 1,25-D 3 -treated PBMCs, addition of exogenous IL-2 resulted in a full reversal of the 1,25-D 3 -mediated Ig inhibition. These data suggest that the inability of IL-2 to reverse the inhibitory effects of 1,25-D 3 on PBMC Ig production is probably a result of a lack of sensitivity of CD8 + T-cells to the antiproliferative and immunoregulatory actions of 1,25-D 3 . This is possibly because of a differential expression of 1,25-D 3 receptors on CD 4+ and CD8 + T-cells. |
Databáze: | OpenAIRE |
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