Lawson C M, Hodgkin P D, Shellam G R
Department of Microbiology, University of Western Australia, Nedlands.
J Gen Virol. 1989 May;70 ( Pt 5):1253-9. doi: 10.1099/0022-1317-70-5-1253.
The ability of mice to survive infection with murine cytomegalovirus (MCMV) is known to be influenced by genes of the major histocompatibility complex (MHC). One hypothesis to account for this association is that MHC-linked resistance to MCMV is an 'immune response' gene effect, caused by differences in the strength of the MHC-restricted T cell response of mouse strains with different MHC haplotypes. Therefore, removal of T cell responses in mouse strains differing only at the MHC should render them equally susceptible to the virus infection. To test this hypothesis, the immunosuppressive drug cyclosporin (CsA) was used to reduce T cell responses in inbred congenic mouse strains carrying either a resistant or susceptible MHC haplotype. CsA reduced the delayed-type hypersensitivity (DTH) response to MCMV in both resistant and susceptible mouse strains to background levels, equivalent to control uninfected mice. CsA treatment had little effect on the susceptibility of C57BL/10 and B10. BR mice to the virus and the differences in susceptibility between these strains remained. In contrast, CsA increased the susceptibility of the genetically susceptible BALB/c mice (H-2d) by 100-fold and increased the susceptibility of resistant BALB.K mice (H-2k) by 15-fold. Thus the H-2-determined difference in susceptibility between these strains was increased after CsA treatment. The results obtained with congenic strains show that MHC-linked resistance patterns to MCMV are not eliminated by CsA and suggest therefore that T cells are not responsible for this phenomenon. Interestingly, the mean time to death was delayed for CsA-treated BALB/c mice compared with untreated mice given equivalent virus doses. In addition, although CsA prevented DTH responses in both genetically susceptible A/J (H-2a) and resistant CBA (H-2k) mice, CsA treatment markedly increased the susceptibility of A/J mice (32-fold) but had little effect on the susceptibility of CBA mice to the virus.
已知小鼠对鼠巨细胞病毒（MCMV）感染的存活能力受主要组织相容性复合体（MHC）基因的影响。解释这种关联的一种假说是，MHC连锁的对MCMV的抗性是一种“免疫反应”基因效应，由具有不同MHC单倍型的小鼠品系的MHC限制性T细胞反应强度差异引起。因此，仅在MHC上存在差异的小鼠品系中去除T细胞反应应使它们对病毒感染同样敏感。为了验证这一假说，使用免疫抑制药物环孢素（CsA）来降低携带抗性或易感MHC单倍型的近交同类系小鼠的T细胞反应。CsA将抗性和易感小鼠品系中对MCMV的迟发型超敏反应（DTH）降低到背景水平，相当于未感染的对照小鼠。CsA处理对C57BL/10和B10.BR小鼠对病毒的易感性影响很小，这些品系之间的易感性差异仍然存在。相反，CsA使基因易感的BALB/c小鼠（H-2d）的易感性增加了100倍，使抗性BALB.K小鼠（H-2k）的易感性增加了15倍。因此，CsA处理后，这些品系之间由H-2决定的易感性差异增加。用同类系小鼠获得的结果表明，CsA并未消除MHC连锁的对MCMV的抗性模式，因此表明T细胞与这种现象无关。有趣的是，与给予等量病毒剂量的未处理小鼠相比，CsA处理的BALB/c小鼠的平均死亡时间延迟。此外，尽管CsA在基因易感的A/J（H-2a）和抗性CBA（H-2k）小鼠中均阻止了DTH反应，但CsA处理显著增加了A/J小鼠的易感性（32倍），而对CBA小鼠对病毒的易感性影响很小。
