Anderson G D, Banerjee S, Luthra H S, David C S
Department of Immunology, Mayo Clinic and Medical School, Rochester, MN 55905.
J Immunol. 1991 Aug 15;147(4):1189-93.
The role of T cell-mediated and humoral immunity to type II collagen has been well documented in collagen-induced arthritis (CIA). Previous work from our laboratory has indicated that genomic deletions of TCR V beta genes may play a role in CIA resistance in mice. This indicated a selectivity of TCR usage by autoreactive T cells in CIA in mice. Certain strains of mice, although having a normal genomic V beta TCR repertoire, can show clonal deletion of peripheral T cells that bear specific V beta gene products in their TCR. These clonally deleted T cells are reactive with self-Ag such as minor lymphocyte stimulation (Mls) Ag. An Mls-congenic strain, BALB.D2.Mlsa, which differs only at the Mls-1 a locus from BALB/c (Mls-1b), was used to examine the effect of clonal deletion of Mls-1a-reactive T cells in CIA. These two strains were crossed to three CIA-susceptible strains, B10.RIII (H-2r, Mls-1b), DBA/1 (H-2q, Mls-1a), and B10.Q (H-2q, Mls-1b), and the crosses were injected with type II collagen. A significantly decreased incidence of arthritis was observed in the (BALB.D2.Mlsa x B10.Q)F1 hybrids, compared with (BALB/c x B10.Q)F1 hybrids, upon immunization with chick type II collagen. The BALB.D2.Mlsa cross mice also had significantly lower levels of antimouse collagen antibodies. Flow cytometric analysis confirmed the clonal deletion of Mls-1a-reactive V beta 8.1, V beta 6, V beta 7, and V beta 9 subsets in the (BALB.D2.Mlsa x B10.Q)F1 hybrids. The study of H-2q/d mice in (BALB.D2.Mlsa x B10.Q) x B10.Q back-crosses demonstrated a significant correlation between CIA resistance and Mls-1a locus. On the other hand, B10.RIII crosses showed only a modest decrease in CIA incidence in the presence of Mls-1a. As expected, all the DBA/1 crosses had an equal incidence of CIA, which was somewhat less than that seen in DBA/1 mice themselves. These studies point out that the Mls-1a locus could play a role in decreasing CIA incidence by clonal deletion of T cells bearing specific V beta TCR, which may be involved in the pathogenesis of CIA. The influence of the clonal deletion of T cells on CIA, and hence the usage of specific V beta TCR by autoreactive anti-type II collagen T cells, however, depends not only on the source of the type II collagen and the MHC class II molecules involved but also on other background genes in mice.
在胶原诱导的关节炎（CIA）中，T细胞介导的免疫和体液免疫对II型胶原的作用已有充分记载。我们实验室先前的研究表明，TCR Vβ基因的基因组缺失可能在小鼠对CIA的抗性中起作用。这表明在小鼠CIA中自身反应性T细胞对TCR的使用具有选择性。某些小鼠品系，尽管具有正常的基因组VβTCR库，但外周T细胞在其TCR中携带特定Vβ基因产物时可出现克隆性缺失。这些克隆性缺失的T细胞可与自身抗原如小淋巴细胞刺激（Mls）抗原发生反应。一个Mls同基因品系BALB.D2.Mlsa，它与BALB/c（Mls-1b）仅在Mls-1a位点不同，用于研究Mls-1a反应性T细胞的克隆性缺失在CIA中的作用。将这两个品系与三个CIA易感品系B10.RIII（H-2r，Mls-1b）、DBA/1（H-2q，Mls-1a）和B10.Q（H-2q，Mls-1b）杂交，并给杂交后代注射II型胶原。在用鸡II型胶原免疫后，与（BALB/c×B10.Q）F1杂种相比，（BALB.D2.Mlsa×B10.Q）F1杂种中关节炎的发生率显著降低。BALB.D2.Mlsa杂交小鼠的抗小鼠胶原抗体水平也显著较低。流式细胞术分析证实了（BALB.D2.Mlsa×B10.Q）F1杂种中Mls-1a反应性Vβ8.1、Vβ6、Vβ7和Vβ9亚群的克隆性缺失。对（BALB.D2.Mlsa×B10.Q）×B10.Q回交后代中的H-2q/d小鼠的研究表明，CIA抗性与Mls-1a位点之间存在显著相关性。另一方面，B10.RIII杂交在存在Mls-1a的情况下，CIA发生率仅略有下降。正如预期的那样，所有DBA/1杂交后代的CIA发生率相同，略低于DBA/1小鼠本身的发生率。这些研究指出，Mls-1a位点可能通过克隆性缺失携带特定VβTCR的T细胞来降低CIA发生率，这些T细胞可能参与CIA的发病机制。然而，T细胞的克隆性缺失对CIA的影响，以及自身反应性抗II型胶原T细胞对特定VβTCR的使用，不仅取决于II型胶原的来源和所涉及的MHC II类分子，还取决于小鼠中的其他背景基因。
