Bauernhofer T, Kuss I, Friebe-Hoffmann U, Baum A S, Dworacki G, Vonderhaar B K, Whiteside T L
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.
Br J Cancer. 2003 Apr 22;88(8):1301-9. doi: 10.1038/sj.bjc.6600860.
Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas - ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.
据报道，催乳素（PRL）可抑制多种细胞类型的凋亡，并在激活过程中作为T细胞上CD25上调的辅助因子。我们研究了乳腺癌患者循环T淋巴细胞上催乳素受体（PRL-R）或白细胞介素-2受体α（IL-2Rα，CD25）表达与其凋亡之间的可能关系。通过多色流式细胞术评估从25例患者、25例正常对照（NC）和3份脐带血样本中获得的外周血单个核细胞的膜联蛋白V结合情况以及CD3(+) T细胞上CD95、CD25和PRL-R的表达。测定患者和对照血浆中PRL、可溶性CD95L（sCD95L）和可溶性IL-2受体（sIL-2R）水平，并将其与T细胞凋亡相关联。还研究了PRL保护T细胞免受各种因素诱导凋亡的能力。乳腺癌患者和NC的T细胞表面PRL-R表达相当，但患者的PRL血浆水平显著较低（P<0.05）。患者中18±11%（平均值±标准差）的CD3(+)细胞结合膜联蛋白V，而NC中为9±6%（P<0.0004）。患者外周循环中CD3(+)Fas(+)和CD3(+)CD25(+)细胞百分比高于NC（分别为P<0.0001和<0.04）。在CD3(+)Fas(+) T细胞比例最高的患者血浆中，可溶性FasL（sFasL）水平最低。患者中大多数发生凋亡的T细胞为CD3(+)CD25(-)，与NC相比，患者中CD3(+)CD25(-)膜联蛋白V(+)细胞比例显著增加（P<0.006）。体外实验中，PRL可保护T细胞免受饥饿诱导或抗CD3抗体诱导的凋亡，但不能保护其免受Fas/FasL依赖性凋亡。这些结果表明，活化T淋巴细胞表面CD25而非PRL-R的表达似乎参与调节Fas/Fas - 配体相互作用，这在一定程度上导致了乳腺癌患者循环中T淋巴细胞凋亡和免疫细胞过度更新。
