Taylor P C, Plater-Zyberk C, Maini R N
Kennedy Institute of Rheumatology, London, GB.
Eur J Immunol. 1995 Mar;25(3):763-9. doi: 10.1002/eji.1830250321.
Collagen-induced arthritis (CIA) can be transferred from DBA/1 to SCID mice when native type II collagen (CII) is administered together with spleen cells, arthritis appearing some 14 days after cell transfer. In the present study, we demonstrate that both donor T- and B-lymphocyte populations play a role in this model, and that arthritis arises in SCID recipients of either murine or bovine native CII. Furthermore, the requirement for administration of soluble native CII can be replaced by subarthritogenic doses of serum from Wistar rats with CIA. In this case a fully developed arthritis appears as early as 2 days after cell transfer. However, protein G-purified IgG from CIA rat serum together with splenocytes from arthritic DBA/1 mice does not transfer arthritis. A key role of B cells in this model appears to be the production of a humoral arthritogenic factor since arthritis can be successfully transferred to SCID mice by CIA rat serum administered together with a B cell-depleted splenocyte population consisting of T cells and donor-histocompatible antigen-presenting cells. By contrast, transfer of disease cannot be achieved by co-administration of CIA rat serum and purified donor T cells, indicating that the presence of donor antigen-presenting cells is a requirement for adoptive transfer of arthritis. We propose that joint damage initiated by arthritogenic product(s) of the B cell lineage releases soluble antigens that are presented to T cells which perpetuate the disease. The finding that arthritis can be generated in SCID recipients of CIA rat serum together with splenocytes from non-arthritic DBA/1 mice immunized with denatured CII supports the hypothesis that T cells with specificity for denatured joint components perpetuate disease initiated by humoral factors.
当天然II型胶原蛋白(CII)与脾细胞一起给予时,胶原诱导的关节炎(CIA)可从DBA/1小鼠转移至SCID小鼠,关节炎在细胞转移后约14天出现。在本研究中,我们证明供体T淋巴细胞和B淋巴细胞群体在该模型中均发挥作用,并且在接受鼠源或牛源天然CII的SCID受体中会出现关节炎。此外,用患CIA的Wistar大鼠的亚致关节炎剂量血清可替代可溶性天然CII的给药。在这种情况下,早在细胞转移后2天就会出现完全发展的关节炎。然而,来自CIA大鼠血清经蛋白G纯化的IgG与患关节炎的DBA/1小鼠的脾细胞一起不能转移关节炎。B细胞在该模型中的关键作用似乎是产生一种体液性致关节炎因子,因为通过将CIA大鼠血清与由T细胞和供体组织相容性抗原呈递细胞组成的B细胞耗竭脾细胞群体一起给药,可成功将关节炎转移至SCID小鼠。相比之下,联合给予CIA大鼠血清和纯化的供体T细胞不能实现疾病转移,这表明供体抗原呈递细胞的存在是关节炎过继转移的必要条件。我们提出,由B细胞系的致关节炎产物引发的关节损伤会释放可溶性抗原,这些抗原呈递给T细胞,从而使疾病持续存在。用变性CII免疫的非关节炎DBA/1小鼠的脾细胞与CIA大鼠血清一起可在SCID受体中引发关节炎,这一发现支持了以下假设:对变性关节成分具有特异性的T细胞会使由体液因子引发的疾病持续存在。