MULTIPLE LOCI GOVERN THE BONE-MARROW-DERIVED IMMUNOREGULATORY MECHANISM CONTROLLING DOMINANT RESISTANCE TO AUTOIMMUNE ORCHITIS
MULTIPLE LOCI GOVERN THE BONE-MARROW-DERIVED IMMUNOREGULATORY MECHANISM CONTROLLING DOMINANT RESISTANCE TO AUTOIMMUNE ORCHITIS
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DOI：
10.1073/pnas.92.12.5684
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发表时间：
1995-06-06
影响因子：
11.1
通讯作者：
TEUSCHER, C
中科院分区：
文献类型：
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作者：
MEEKER, ND;HICKEY, WF;TEUSCHER, C
赋予对自身免疫的显性抗性的免疫调节基因的存在是有据可查的。为了更好地理解这些基因的作用的性质和机制，我们利用自身免疫性睾丸炎的小鼠模型作为原型。用抗睾丸炎品系DBA/2 J与睾丸炎敏感品系BALB/cByJ杂交，其F-1代完全抗睾丸炎，即By;使用相互辐射骨髓嵌合体，介导这种抗性的功能成分被定位到骨髓衍生的隔室，抗性不是低剂量辐射或环磷酰胺的功能（20 mg/kg）敏感的免疫调节细胞，但可以通过致敏的脾细胞过继转移。基因组排阻作图确定了三个控制抗性表型的基因座。Orchil定位于11号染色体，而Orch 4和Orch 5分别定位于1号染色体的端粒和着丝粒区域。所有三个基因都与许多免疫学相关的候选基因座连锁。然而，最重要的是Orch 3与Idd 4的连锁和Orch 5与Idd 5的连锁，两个易感基因在非肥胖糖尿病小鼠的自身免疫性胰岛素依赖型1型糖尿病中起作用。
The existence of immunoregulatory genes conferring dominant resistance to autoimmunity is well documented, In an effort to better understand the nature and mechanisms of action of these genes, we utilized the murine model of autoimmune orchitis as a prototype. When the orchitis-resistant strain DBA/2J is crossed with the orchitis-susceptible strain BALB/cByJ, the F-1 hybrid is completely resistant to the disease, By; using reciprocal radiation bone marrow chimeras, the functional component mediating this resistance was mapped to the bone marrow-derived compartment, Resistance is not a function of either low-dose irradiation- or cyclophosphamide (20 mg/kg)-sensitive immunoregulatory cells, but can be adoptively transferred by primed splenocytes. Genome exclusion mapping identified three loci controlling the resistant phenotype. Orchil maps to chromosome 11, whereas Orch4 and Orch5 map to the telomeric and centromeric regions of chromosome 1, respectively, All three genes are linked to a number of immunologically relevant candidate loci, Most significant, however, is the linkage of Orch3 to Idd4 and Orch5 to Idd5, two susceptibility genes which play a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse.