Kim Byung S, Mohindru Mani, Kang Bongsu, Kang Hyun Seok, Palma Joann P
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Il 60611, USA.
J Neurosci Res. 2005 Sep 15;81(6):846-56. doi: 10.1002/jnr.20611.
We have investigated the potential effects of H-2 and T-cell receptor (TCR) V beta family genes on induction of T-cell immunity and susceptibility to virally induced demyelinating disease by using BALB.S (H-2K(s)A(s)D(s)) and BALB.S 3 R (H-2K(s)A(s)D(d)/L(d)) mice. These parameters were compared with those of highly susceptible SJL/J (H-2K(s)A(s)D(s)) mice that contain only one-half of TCR V beta family genes compared with the above-mentioned strains. Our results demonstrate that BALB.S but not BALB.S 3 R mice are susceptible similar to SJL/J mice. Although the level of CD4(+) T-cell infiltration to the CNS was elevated in susceptible mice, virus-specific immune responses restricted with H-2(s) were similar in these mice. No preferential use of V beta families associated with differences in the major histocompatibility complex (MHC) components was apparent. However, the pattern and sequence of CDR 3 distribution shows T-cell clonal accumulation in the CNS associated with the H-2 components. Further anti-CD8 antibody treatment of resistant BALB.S 3 R mice abrogated resistance to demyelinating disease, indicating that CD8(+) T cells restricted with H-2D(d)/L(d) are most likely to exert resistance in BALB.S 3 R mice. These studies indicated that TCR V beta and MHC class II genes are the secondary to a particular MHC class I gene expression in susceptibility to virally induced demyelinating disease.
我们通过使用BALB.S（H-2K(s)A(s)D(s)）和BALB.S 3R（H-2K(s)A(s)D(d)/L(d)）小鼠，研究了H-2和T细胞受体（TCR）Vβ家族基因对T细胞免疫诱导以及对病毒诱导的脱髓鞘疾病易感性的潜在影响。将这些参数与高度易感的SJL/J（H-2K(s)A(s)D(s)）小鼠的参数进行比较，与上述品系相比，SJL/J小鼠仅含有一半的TCR Vβ家族基因。我们的结果表明，BALB.S小鼠而非BALB.S 3R小鼠与SJL/J小鼠一样易感。尽管易感小鼠中CD4(+) T细胞向中枢神经系统的浸润水平升高，但这些小鼠中受H-2(s)限制的病毒特异性免疫反应相似。与主要组织相容性复合体（MHC）成分差异相关的Vβ家族没有明显的优先使用情况。然而，CDR 3分布的模式和序列显示，中枢神经系统中T细胞克隆积累与H-2成分相关。对具有抗性的BALB.S 3R小鼠进一步用抗CD8抗体治疗消除了对脱髓鞘疾病的抗性，表明受H-2D(d)/L(d)限制的CD8(+) T细胞最有可能在BALB.S 3R小鼠中发挥抗性作用。这些研究表明，在对病毒诱导的脱髓鞘疾病的易感性方面，TCR Vβ和MHC II类基因相对于特定的MHC I类基因表达是次要的。
