Lukić Ivan Kresimir, Kovacić Natasa, Katavić Vedran, Grcević Danka, Ivcević Sanja, Marusić Ana
Department of Anatomy, Zagreb University School of Medicine, Salata 11, Zagreb HR-10000, Croatia.
Cell Immunol. 2005 Feb;233(2):133-9. doi: 10.1016/j.cellimm.2005.04.010.
We have previously shown that mice with generalised lymphoproliferative disorder (gld) have increased bone mass in addition to autoimmune disease characterised by the accumulation of double negative (dn) T lymphocytes (CD3(+)CD4(-)CD8(-)CD45R(+)). To further explore the association of the immune disorder with the bone phenotype of gld mice, we established parabiotic circulation between gld and wild-type animals (C57BL/6, B6). One week after the surgery, the proportion of dn T lymphocytes increased in peripheral blood, bone marrow, spleen, and lymph nodes of wild-type members of the B6-gld parabiotic pair and decreased in tissues of gld pair members. The mixing of cells continued during four weeks of parabiosis. Number of osteoclast-like (OCL) cells in bone marrow cultures from a wild-type member of B6-gld parabiotic pair at the end of the first week decreased from 266+/-52 to 120+/-5OCL/cm(2), P<0.05, comparable with gld mice (99+/-21OCL/cm(2)), while the number of osteoblast colonies did not change. After four weeks, number of OCL cells formed from the bone marrow of B6 parabiotic mice was still similar to the number of OCL cells in their gld counterparts (150+/-18 and 131+/-24OCL/cm(2), respectively). In addition, the number of osteoblast colonies in B6 members of B6-gld parabiotic pairs increased (from 6+/-2 to 18+/-1colonies/cm(2), P<0.05) thus resembling the cell cultures of gld mice (18+/-1colonies/cm(2)). Taken together, these data show that the circulation of cells, including dn T lymphocytes established by parabiosis confers the osteoclast and osteoblast phenotype of gld to wild-type animals.
我们之前已经表明,患有全身性淋巴增殖性疾病(gld)的小鼠除了患有以双阴性(dn)T淋巴细胞(CD3(+)CD4(-)CD8(-)CD45R(+))积累为特征的自身免疫疾病外,骨量也有所增加。为了进一步探究免疫紊乱与gld小鼠骨表型之间的关联,我们在gld和野生型动物(C57BL/6,B6)之间建立了联体循环。手术后一周,B6-gld联体对中野生型成员的外周血、骨髓、脾脏和淋巴结中dn T淋巴细胞的比例增加,而gld对成员的组织中该比例下降。联体共生的四周内细胞混合持续存在。在第一周结束时,B6-gld联体对中野生型成员骨髓培养物中的破骨细胞样(OCL)细胞数量从266±52降至120±5OCL/cm²,P<0.05,与gld小鼠(99±21OCL/cm²)相当,而成骨细胞集落数量没有变化。四周后,B6联体小鼠骨髓形成的OCL细胞数量仍与其gld对应物的OCL细胞数量相似(分别为150±18和131±24OCL/cm²)。此外,B6-gld联体对中B6成员的成骨细胞集落数量增加(从6±2增至18±1集落/cm²,P<0.05),因此类似于gld小鼠的细胞培养物(18±1集落/cm²)。综上所述,这些数据表明,通过联体共生建立的包括dn T淋巴细胞在内的细胞循环将gld的破骨细胞和成骨细胞表型赋予了野生型动物。