Durandy A, Le Deist F, Emile J F, Debatin K, Fischer A
Institut National de la Santé et de la Recherche Médicale U 429, Hôpital Necker-Enfants Malades, Paris, France.
Eur J Immunol. 1997 Feb;27(2):538-43. doi: 10.1002/eji.1830270227.
Epstein-Barr virus (EBV) can induce uncontrolled B lymphocyte proliferation leading to fatal lymphoma in immunocompromised patients. The sensitivity to apoptosis of B lymphoid cell lines (LCL) derived from EBV-induced lymphoproliferative disorders was investigated. In vitro and in vivo, these B LCL strongly express CD95/Apo-1/fas antigen and undergo apoptosis upon stimulation with anti-Apo-1 monoclonal antibody. When inoculated into severe-combined immunodeficient (scid) mice, human B cells lines developed into rapidly growing tumors. Administration of an agonistic anti-Apo-1 antibody significantly delayed tumor progression. Relapses were frequent, but were not caused by selection of resistant B cells, since B cells from relapsing tumors underwent apoptosis on re-exposure. Induction of apoptosis by an anti-C95/Apo-1/fas-specific antibody could be applied for therapy of EBV-induced B cell tumors and contribute to our understanding of the mechanisms of T cell-mediated elimination of EBV lymphomas in immunodeficient patients.
爱泼斯坦-巴尔病毒(EBV)可诱导B淋巴细胞不受控制地增殖,导致免疫功能低下患者发生致命性淋巴瘤。我们研究了源自EBV诱导的淋巴增殖性疾病的B淋巴母细胞系(LCL)对凋亡的敏感性。在体外和体内,这些B-LCL强烈表达CD95/Apo-1/fas抗原,并在抗Apo-1单克隆抗体刺激下发生凋亡。当接种到严重联合免疫缺陷(scid)小鼠体内时,人B细胞系发展成快速生长的肿瘤。给予激动性抗Apo-1抗体可显著延迟肿瘤进展。复发很常见,但不是由耐药B细胞的选择引起的,因为复发肿瘤中的B细胞在再次暴露时会发生凋亡。抗C95/Apo-1/fas特异性抗体诱导凋亡可用于治疗EBV诱导的B细胞肿瘤,并有助于我们理解免疫缺陷患者中T细胞介导的EBV淋巴瘤消除机制。