Baraz L, Khazanov E, Condiotti R, Kotler M, Nagler A
Department of Bone Marrow Transplantation, Hadassah University Hospital, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Bone Marrow Transplant. 1999 Jul;24(2):179-89. doi: 10.1038/sj.bmt.1701825.
Natural killer (NK) cells (CD3-/CD16+/CD56+ lymphocytes) play an important role in early immune defense against viral infection, a fact which is of prime significance for heavily immunosuppressed patients after bone marrow transplantation. In this study we demonstrate that NK cells preferentially lyse human colon adenocarcinoma (Colo-205) tumor cells infected with herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV) and autologous T cells infected with VV. This phenomenon was assessed by the viral infectious center (IC) method and compared with the results obtained by means of the standard 51Cr-release assay. Using the IC assay, we found that NK cells lyse virus infected cells at an early stage of infection, thereby preventing viral dissemination to neighboring cells. 51Cr-release assay verified by propidium iodide (PI) penetration showed that the early effects of NK mediated anti-viral activity are not the result of membrane damage. The effect of NK cells on HSV-1 infected Colo-205 cells appears to be independent of the level of expression of major histocompatibility complex (MHC) class I molecules while the killing of autologous VV-infected T cells correlates with a reduction in MHC class I expression. Our results suggest that additional factors besides MHC play a role in the regulation of NK cell-mediated lysis of virus infected cells. This may be of clinical importance in patients who are heavily immunosuppressed after bone marrow transplantation.
自然杀伤(NK)细胞(CD3-/CD16+/CD56+淋巴细胞)在针对病毒感染的早期免疫防御中发挥着重要作用,这一事实对于骨髓移植后严重免疫抑制的患者至关重要。在本研究中,我们证明NK细胞优先裂解感染1型单纯疱疹病毒(HSV-1)和痘苗病毒(VV)的人结肠腺癌(Colo-205)肿瘤细胞以及感染VV的自体T细胞。通过病毒感染中心(IC)方法评估了这一现象,并与通过标准51Cr释放试验获得的结果进行了比较。使用IC试验,我们发现NK细胞在感染早期裂解病毒感染的细胞,从而防止病毒传播到邻近细胞。经碘化丙啶(PI)渗透验证的51Cr释放试验表明,NK介导的抗病毒活性的早期作用不是膜损伤的结果。NK细胞对HSV-1感染的Colo-205细胞的作用似乎与主要组织相容性复合体(MHC)I类分子的表达水平无关,而对自体VV感染的T细胞的杀伤与MHC I类表达的降低相关。我们的结果表明,除MHC外的其他因素在调节NK细胞介导的病毒感染细胞裂解中起作用。这对于骨髓移植后严重免疫抑制的患者可能具有临床重要性。