Differential roles of B cells and IFN-γ-secreting CD4+ T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice
Differential roles of B cells and IFN-γ-secreting CD4+ T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice
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DOI：
10.1099/0022-1317-82-4-845
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发表时间：
2001-04-01
影响因子：
3.8
通讯作者：
Eriksson, K
中科院分区：
文献类型：
--
作者：
Harandi, AM;Svennerholm, B;Eriksson, K
已阐明B、CD4(+)T细胞和CD8(+)T细胞在初次生殖器感染减毒单纯疱疹病毒2型(HSV-2)以及利用淋巴细胞缺陷小鼠对强毒HSV-2攻击的保护性免疫形成中的作用。在初次接种减毒胸苷激酶缺陷(TK-)HSV-2后，B细胞缺陷(MU MT)小鼠出现局部病毒血症和一过性生殖器炎症，提示B细胞在局部感染和炎症的先天控制中发挥作用。自然抗体参与了这一过程，因为被动地将正常血清转移到MU MT小鼠体内显著减少了HSV-2 TK在阴道腔中的脱落，尽管它不影响随后的炎症。在HSV-2免疫的野生型、CD8(+)T细胞缺陷小鼠和Mu MT小鼠中，观察到了对HSV-2致死性攻击的保护作用，体外表现为强烈的病毒特异性干扰素-γ反应，在体内表现为迟发型超敏反应(DTH)。相比之下，CD4(+)T细胞缺陷(CD4(-/-))小鼠的HSV-2特异性干扰素-γ的产生和DTH反应受损，并迅速屈服于生殖器HSV-2的攻击。然而，重组干扰素-γ可在HSV-2免疫的CD4(-/-)小鼠中诱导对HSV-2的保护性反应，这些结果提示，分泌干扰素-γ的CD4(+)T细胞对HSV-2再次感染的免疫保护至关重要，而B细胞/天然抗体在初次感染的先天控制中具有抗病毒和抗炎作用。
The role of B, CD4(+) T and CD8(+) T cells in both primary genital infection with attenuated herpes simplex virus type 2 (HSV-2) and development of protective immunity to a later challenge with virulent HSV-2 using lymphocyte-deficient mice has been elucidated. Following primary inoculation with attenuated thymidine kinase-deficient (TK-) HSV-2, B cell-deficient (mu MT) mice developed a local viraemia and transient genital inflammation, suggesting a role for B cells in the innate control of local infection and inflammation. Natural antibodies are implicated in this process, as passive transfer of normal serum into mu MT mice significantly reduced HSV-2 TK- shedding in the vaginal lumen, although it did not affect subsequent inflammation. Protection against lethal HSV-2 challenge was noted in HSV-2-vaccinated wild-type, CD8(+) T cell-deficient and mu MT mice and was characterized by strong virus-specific IFN-gamma responses in vitro and delayed type hypersensitivity (DTH) responses in vivo. In contrast, CD4(+) T cell-deficient (CD4(-/-)) mice had impaired HSV-2-specific IFN-gamma production and DTH responses and succumbed rapidly to genital HSV-2 challenge. However, protective responses to HSV-2 could be induced in HSV-2-vaccinated CD4(-/-) mice by treatment with recombinant IFN-gamma, Taken together, these results suggest that CD4(+) T cells secreting IFN-gamma are critical for immune protection against lethal genital HSV-2 re-infection, whereas B cells/natural antibodies have anti-viral and -inflammatory effects in the innate control of a primary infection.