Permar Sallie R, Klumpp Sherry A, Mansfield Keith G, Carville Angela A L, Gorgone Darci A, Lifton Michelle A, Schmitz Jörn E, Reimann Keith A, Polack Fernando P, Griffin Diane E, Letvin Norman L
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
J Infect Dis. 2004 Sep 1;190(5):998-1005. doi: 10.1086/422846. Epub 2004 Jul 26.
The development of an improved vaccine for controlling measles virus (MV) infections in the developing world will require an understanding of the immune mechanisms responsible for the clearance of this virus. To evaluate the role of humoral immunity in the containment of MV, rhesus monkeys were treated at the time of MV challenge with either anti-CD20 monoclonal antibody (MAb) infusion, to deplete B lymphocytes, or both anti-CD20 and anti-CD8 MAb, to deplete both B lymphocytes and CD8+ effector T lymphocytes. Although the MV-specific antibody response in CD20+ lymphocyte-depleted monkeys was delayed by >1 week, the kinetics of MV clearance did not differ from those for monkeys that received control MAb. Furthermore, unusual clinical sequelae of MV infection were not observed in these monkeys. In contrast, MV-infected rhesus monkeys depleted of both CD20+ and CD8+ lymphocytes had a prolonged duration of viremia and developed a desquamating skin rash. These findings indicate that humoral immunity plays a limited role in the control of MV replication in an MV-naive individual and suggest that new measles vaccination strategies should focus on the elicitation of cell-mediated immune responses, in addition to neutralizing antibodies, to facilitate rapid elimination of locally replicating virus.
要开发一种用于控制发展中国家麻疹病毒(MV)感染的改良疫苗,需要了解负责清除该病毒的免疫机制。为了评估体液免疫在控制MV中的作用,在MV攻击时,对恒河猴进行治疗,要么输注抗CD20单克隆抗体(MAb)以耗尽B淋巴细胞,要么同时输注抗CD20和抗CD8 MAb以耗尽B淋巴细胞和CD8 +效应T淋巴细胞。尽管CD20 +淋巴细胞耗竭的猴子中MV特异性抗体反应延迟超过1周,但MV清除的动力学与接受对照MAb的猴子并无差异。此外,在这些猴子中未观察到MV感染的异常临床后遗症。相比之下,CD20 +和CD8 +淋巴细胞均被耗尽的MV感染恒河猴病毒血症持续时间延长,并出现了脱屑性皮疹。这些发现表明,体液免疫在初次接触MV的个体中对控制MV复制的作用有限,并表明新的麻疹疫苗接种策略除了中和抗体外,还应侧重于激发细胞介导的免疫反应,以促进快速清除局部复制的病毒。