title: Exogenous interleukin-2 does not reverse the immunoinhibitory effects of 1,25-dihydroxyvitamin D3 on human peripheral blood lymphocyte immunoglobulin production.
abstract: 1,25-Dihydroxyvitamin D3 (1,25-D3) 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-D3. Previous studies have also shown that the CD4+ T-cell subset is more sensitive to the antiproliferative actions of 1,25-D3 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-D3-treated PBMCs allowed the cells to overcome the 1,25-D3 suppressive effect on cell proliferation. However, exogenous IL-2 did not overcome the 1,25-D3-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-D3, 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-D3 inhibitory effect on Ig synthesis in PBMCs. In other experiments, when CD8+ cells were removed from mitogen-stimulated, 1,25-D3-treated PBMCs, addition of exogenous IL-2 resulted in a full reversal of the 1,25-D3-mediated Ig inhibition. These data suggest that the inability of IL-2 to reverse the inhibitory effects of 1,25-D3 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-D3. This is possibly because of a differential expression of 1,25-D3 receptors on CD4+ and CD8+ T-cells.
authors.affiliation: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
authors.forename: S C
authors.initials: SC
authors.lastname: Jordan
authors.forename: J M
authors.initials: JM
authors.lastname: Lemire
authors.forename: R S
authors.initials: RS
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Toyoda
authors.forename: J S
authors.initials: JS
authors.lastname: Adams
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007166:Immunosuppressive Agents; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; D002117:Calcitriol