Analysis of TNF-receptor and ligand superfamily molecules in patients with lymphoproliferative disease of granular lymphocytes

作     者：Zambello, R Trentin, L Facco, M Siviero, M Galvan, S Piazza, F Perin, A Agostini, C Semenzato, G 

作者机构：Univ Padua Dipartimento Med Clin & Sperimentale Immunol Clin Sch MedClin Immunol Branch I-35128 Padua Italy Vicenza Hosp Div Hematol Vicenza Italy 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第96卷第2期

页      面：647-654页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：抗原 CD3/分析 抗原 CD30/分析 抗原 CD40/分析 抗原 CD95/分析 细胞分裂 细胞毒性 免疫 流式细胞术 白细胞介素2/药理学 杀伤细胞 天然/免疫学 杀伤细胞 天然/病理学 配体 淋巴细胞/免疫学 淋巴细胞/病理学 淋巴组织增殖性疾病/免疫学 淋巴组织增殖性疾病/病理学 受体 IgG/分析 受体 肿瘤坏死因子/分析 逆转录聚合酶链反应 T淋巴细胞/免疫学 T淋巴细胞/病理学 肿瘤坏死因子α/分析 成年人 老年人 女(雌)性 人类 男(雄)性 中年人 

摘      要：In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L;CD40/CD40L;CD27/CD70;Fas [CD95]/FasL[CD95L]), Fourteen patients were characterized by a proliferation of granular lymphocytes (GLs) expressing the CD3(+)CD16(+) phenotype, whereas 7 cases showed the CD3(-)CD16(+) CD56 +/- phenotype, Our data show that both CD3(+) and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95 antigens;this pattern Is usually associated with the lack of CD27 and CD30L antigens expression. CD95L was demonstrated in the cytoplasm in 14 of 21 cases by flow cytometry, but a definite signal was demonstrated in all cases studied using polymerase chain reaction analysis. On functional grounds, a stimulatory activity on rIL-2 mediated redirected-cytotoxicity against Fc gamma+ P815 targets was demonstrated with anti-CD30, CD40, CD40L, CD70, CD95, and CD95L mAbs, although resting cells were unable to exhibit significant redirected-cell lysis. The addition of anti-CD30, CD30L, CD40, CD40L, CD95, and CD95L mAbs did not show any significant effect on cell proliferation at resting conditions or after rIL-2 stimulation, whereas anti-CD70 mAb mediated cell proliferation in 6 of 10 cases tested. This figure was not related to an increase in apoptotic cells, as investigated by Annexin-V expression. Our data indicate that both CD3(+) and CD3(-) GLs are equipped with different costimulatory antigens, supporting the concept that these cells are in vivo activated and suggesting that these molecules might play a role in the cytotoxic mechanisms of GLs, (C) 2000 by The American Society of Hematology.