Jordan S C, Lemire J M, Sakai R S, Toyoda M, Adams J S
Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Mol Immunol. 1990 Jan;27(1):95-100. doi: 10.1016/0161-5890(90)90064-7.
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.
已知1,25 - 二羟基维生素D3（1,25 - D3）对人外周血单个核细胞（PBMC）功能具有强大的抑制作用。先前的实验表明，在细胞培养物中添加白细胞介素 - 2（IL - 2）可逆转1,25 - D3的抗增殖作用。先前的研究还表明，CD4 + T细胞亚群比CD8 + T细胞对1,25 - D3的抗增殖作用更敏感。本研究的目的是确定外源性IL - 2是否能逆转丝裂原激活的PBMC培养物以及荧光素激活细胞分选（FACS）实验中的抗增殖和免疫抑制作用（抑制Ig产生），在FACS实验中，在用/不用添加外源性IL - 2的情况下，在丝裂原刺激之前从PBMC中去除CD8 + T细胞。在这些研究中，向丝裂原激活的、经1,25 - D3处理的PBMC中添加IL - 2可使细胞克服1,25 - D3对细胞增殖的抑制作用。然而，外源性IL - 2并未克服1,25 - D3介导的对PBMC Ig产生的抑制作用。使用FACS淋巴细胞群体（CD4 +、CD8 +和B细胞），我们发现与自体B细胞共培养时，CD4 + T细胞导向的Ig合成可被1,25 - D3处理细胞抑制，但通过添加外源性IL - 2可使Ig合成恢复到接近正常水平。这与IL - 2无法逆转1,25 - D3对PBMC中Ig合成的抑制作用形成鲜明对比。在其他实验中，当从经丝裂原刺激、1,25 - D3处理的PBMC中去除CD8 +细胞时，添加外源性IL - 2可导致1,25 - D3介导的Ig抑制作用完全逆转。这些数据表明，IL - 2无法逆转1,25 - D3对PBMC Ig产生的抑制作用可能是由于CD8 + T细胞对1,25 - D3的抗增殖和免疫调节作用缺乏敏感性所致。这可能是因为CD4 +和CD8 + T细胞上1,25 - D3受体的表达存在差异。
