Schurmans S, Gonzalez A, Revilla C, Ramos A, Lambert P H, Merino J
WHO Immunology Research and Training Center, Department of Pathology, CMU, University of Geneva.
Eur J Immunol. 1994 Apr;24(4):985-90. doi: 10.1002/eji.1830240431.
The injection of (C57BL/6 x BALB/c)F1 spleen cells into newborn BALB/c mice results in the induction of a specific cytotoxic T lymphocyte (CTL) tolerance to the alloantigens. On the contrary, alloreactive CD4+ T cells persist in the host and are still able to activate autoreactive F1 B cells to produce autoantibodies. This state of "split tolerance" is closely associated with the development of a lupus-like autoimmune syndrome. The LFA-1 integrin plays a relevant role in homing, intercellular adhesion and tranduction of co-stimulatory signals in leukocytes. Because of the beneficial effects of anti-LFA-1 monoclonal antibodies (mAb) treatment in various models of organ transplantation and autoimmune disease, we have investigated if such a treatment could interfere with the induction of neonatal tolerance or the development of the autoimmune syndrome in F1 cell-injected newborn mice. For this purpose, BALB/c mice neonatally injected with F1 cells were treated from day 1 up to day 15 with a non-cytotoxic anti-LFA-1 (CD11a) mAb. Anti-LFA-1 mAb treatment interfered with the persistence of a stable chimerism and with the establishment of CTL tolerance, as shown by rejection of allogeneic skin grafts and F1 B cells, and by a normal in vitro CTL activity against the corresponding alloantigens. As a consequence, these mice did not develop the characteristic autoimmune features seen in close association with an effective induction of CTL tolerance to alloantigens. These results stress the importance of the interactions between LFA-1 and its ligands during the neonatal induction of tolerance to alloantigens.
将（C57BL/6×BALB/c）F1脾细胞注射到新生BALB/c小鼠体内会诱导对同种异体抗原的特异性细胞毒性T淋巴细胞（CTL）耐受。相反，同种异体反应性CD4 + T细胞在宿主体内持续存在，并且仍然能够激活自身反应性F1 B细胞产生自身抗体。这种“分裂耐受”状态与狼疮样自身免疫综合征的发展密切相关。LFA-1整合素在白细胞的归巢、细胞间粘附以及共刺激信号的转导中发挥相关作用。由于抗LFA-1单克隆抗体（mAb）治疗在各种器官移植和自身免疫性疾病模型中具有有益效果，我们研究了这种治疗是否会干扰新生小鼠注射F1细胞后新生儿耐受的诱导或自身免疫综合征的发展。为此，从第1天到第15天，用非细胞毒性抗LFA-1（CD11a）mAb对新生时注射F1细胞的BALB/c小鼠进行治疗。抗LFA-1 mAb治疗干扰了稳定嵌合体的持续存在以及CTL耐受的建立，这表现为同种异体皮肤移植和F1 B细胞的排斥反应，以及针对相应同种异体抗原的正常体外CTL活性。因此，这些小鼠没有出现与有效诱导对同种异体抗原的CTL耐受密切相关的特征性自身免疫特征。这些结果强调了LFA-1与其配体之间的相互作用在新生儿诱导对同种异体抗原耐受过程中的重要性。
