Morrison L A, Knipe D M
Department of Microbiology and Molecular Genetics, Harvard medical School, Boston, Massachusetts 02115, USA.
Virology. 1997 Dec 22;239(2):315-26. doi: 10.1006/viro.1997.8884.
Replication-defective mutants of herpes simplex virus 1 (HSV-1) elicit immune responses in mice that reduce acute and latent infection after corneal challenge and are protective against development of disease. To understand the basis for the protective immunity induced by this new form of immunization, we investigated the contribution of various components of the immune response to protection against corneal infection and disease. Passive transfer of sera from mice immunized with the replication-defective mutant virus, d301, its parental HSV-1 strain, or uninfected cell lysate was used to examine the role of antibody. Despite posttransfer neutralizing antibody titers equivalent to those in control mice directly immunized with mutant virus, recipients of immune serum showed no reductions in primary replication in the eye, keratitis, or latent infection of the nervous system. However, immune serum protected mice from encephalitis and death. To examine the contribution of T cell subsets to protection, mice were immunized once with mutant virus and then were depleted in vivo of CD4+ or CD8+ T cells prior to corneal challenge. CD4 depletion resulted in higher titers of challenge virus in the eye at 3 to 4 days after challenge compared to control mice. Latent infection of the nervous system was increased by depletion of CD4+ T cells but not by depletion of CD8+ T cells keratitis developed only in a portion of the CD8+ T cell-depleted mice, suggesting that an immunopathologic potential of CD4+ T cells is held in check when immune CD8+ T cells are also present. Taken together, these data support a role for antibody induced by immunization with a replication-defective virus principally in protecting the central nervous system from disease, roles for CD4+ T cells in reducing primary replication in the eye and protecting against latent infection of the nervous system, and a role for CD8+ T cells in regulating the immunopathologic activity of CD4+ T cells.
单纯疱疹病毒1型（HSV-1）的复制缺陷型突变体在小鼠中引发免疫反应，可降低角膜感染后的急性和潜伏感染，并预防疾病的发生。为了解这种新型免疫诱导的保护性免疫的基础，我们研究了免疫反应的各种成分对预防角膜感染和疾病的作用。用复制缺陷型突变病毒d301、其亲本HSV-1毒株或未感染细胞裂解物免疫的小鼠血清进行被动转移，以检测抗体的作用。尽管转移后中和抗体滴度与直接用突变病毒免疫的对照小鼠相当，但免疫血清的接受者在眼部的初次复制、角膜炎或神经系统潜伏感染方面并未减少。然而，免疫血清可保护小鼠免受脑炎和死亡。为检测T细胞亚群对保护作用的贡献，小鼠先用突变病毒免疫一次，然后在角膜感染前在体内清除CD4+或CD8+T细胞。与对照小鼠相比，清除CD4后，感染后3至4天眼部的攻击病毒滴度更高。CD4+T细胞的清除增加了神经系统的潜伏感染，但CD8+T细胞的清除并未增加，只有一部分清除CD8+T细胞的小鼠发生了角膜炎, 这表明当免疫CD8+T细胞也存在时，CD4+T细胞的免疫病理潜能受到抑制。综上所述，这些数据支持了以下观点：用复制缺陷型病毒免疫诱导的抗体主要在保护中枢神经系统免受疾病方面发挥作用；CD4+T细胞在减少眼部初次复制和预防神经系统潜伏感染方面发挥作用；CD8+T细胞在调节CD4+T细胞的免疫病理活性方面发挥作用。
