Stiles Linda N, Hosking Martin P, Edwards Robert A, Strieter Robert M, Lane Thomas E
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Eur J Immunol. 2006 Mar;36(3):613-22. doi: 10.1002/eji.200535509.
Lymphocyte infiltration into the central nervous system (CNS) following viral infection represents an important component of host defense and is required for control of viral replication. However, the mechanisms governing inflammation in response to viral infection of the CNS are not well understood. Following intracranial (i.c.) infection of susceptible mice with mouse hepatitis virus (MHV), mice develop an acute encephalomyelitis followed by a chronic demyelinating disease. The CXC chemokine ligand 10 (CXCL10) is expressed following MHV infection and signals T cells to migrate into the CNS. The functional contribution of the CXCL10 receptor CXCR3 in host defense and disease in response to MHV infection was evaluated. The majority of CD4+ and CD8+ T cells infiltrating the CNS following MHV infection express CXCR3. Administration of anti-CXCR3 antibody reduced CD4+ T cell infiltration (p<or=0.05), while CD8+ T cell trafficking was not affected. Anti-CXCR3 treatment during chronic disease correlated with improved motor skills and reduced demyelination. The selective effect of anti-CXCR3 treatment on CD4+ T cells was not the result of either reduced proliferation or modulation in chemokine receptor gene expression. Therefore, CXCR3 signaling has a non-redundant role in T cell subset trafficking in response to viral infection.
病毒感染后淋巴细胞浸润中枢神经系统（CNS）是宿主防御的重要组成部分，也是控制病毒复制所必需的。然而，中枢神经系统病毒感染后炎症反应的调控机制尚不清楚。用小鼠肝炎病毒（MHV）颅内（i.c.）感染易感小鼠后，小鼠会发展为急性脑脊髓炎，随后出现慢性脱髓鞘疾病。CXC趋化因子配体10（CXCL10）在MHV感染后表达，并向T细胞发出迁移至中枢神经系统的信号。评估了CXCL10受体CXCR3在宿主防御以及对MHV感染的疾病反应中的功能作用。MHV感染后浸润中枢神经系统的大多数CD4+和CD8+ T细胞表达CXCR3。给予抗CXCR3抗体可减少CD4+ T细胞浸润（p≤0.05），而CD8+ T细胞的迁移不受影响。慢性疾病期间的抗CXCR3治疗与运动技能改善和脱髓鞘减少相关。抗CXCR3治疗对CD4+ T细胞的选择性作用不是增殖减少或趋化因子受体基因表达调节的结果。因此，CXCR3信号在病毒感染后T细胞亚群迁移中具有非冗余作用。
