Suzuki J, Isobe M, Izawa A, Takahashi W, Yamazaki S, Okubo Y, Amano J, Sekiguchi M
Department of Internal Medicine I, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Transpl Immunol. 1999 Mar;7(1):65-72. doi: 10.1016/s0966-3274(99)80021-5.
Administration of anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody (mAb) plus anti-lymphocyte function associated antigen (LFA)-1 mAb induces tolerance in murine cardiac transplantation, while anti-vascular cell adhesion molecule (VCAM)-1 mAb plus anti-very late antigen (VLA)-4 mAb administration prolongs graft survival, but leads to tolerance only in some cases. BALB/c mice hearts were transplanted into C3H/He recipients. Each combination of anti-VCAM-1 plus anti-VLA-4 mAbs (100 microg each/day, i.p.) or anti-ICAM-1 plus anti-LFA-1 mAbs (50 microg each/day, i.p.) was administered for 5 days. For control study, third group mice received daily with FK506 administration (1 mg/kg/day). The cardiac allografts and recipients' spleens were harvested on day 7; the expression of cytokines were detected using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR. Th2 cytokines (IL-4 and IL-10) were markedly enhanced and Th1 cytokines (IFN-gamma and IL-2) were suppressed in recipients treated with anti-ICAM-1 mAb plus anti-LFA-1 mAb, while poor Th2 cytokine expression allowed persistent Th1 cytokine expression in recipient mice with anti-VCAM-1 mAb plus anti-VLA-4 mAb treatment. Both Th1 and Th2 cytokine expression was suppressed in FK506-treated mice. It is concluded that immunological tolerance and prolonged graft survival induced by blocking cell adhesion is regulated by different cytokine expression.
给予抗细胞间黏附分子（ICAM）-1单克隆抗体（mAb）加抗淋巴细胞功能相关抗原（LFA）-1 mAb可诱导小鼠心脏移植耐受，而给予抗血管细胞黏附分子（VCAM）-1 mAb加抗极迟抗原（VLA）-4 mAb可延长移植物存活时间，但仅在某些情况下导致耐受。将BALB/c小鼠的心脏移植到C3H/He受体中。抗VCAM-1加抗VLA-4 mAb（各100μg/天，腹腔注射）或抗ICAM-1加抗LFA-1 mAb（各50μg/天，腹腔注射）的每种组合给药5天。作为对照研究，第三组小鼠每天给予FK506（1mg/kg/天）。在第7天收获心脏异体移植物和受体脾脏；使用免疫组织化学、逆转录-聚合酶链反应（RT-PCR）和原位RT-PCR检测细胞因子的表达。在用抗ICAM-1 mAb加抗LFA-1 mAb治疗的受体中，Th2细胞因子（IL-4和IL-10）明显增强，Th1细胞因子（IFN-γ和IL-2）受到抑制，而在用抗VCAM-1 mAb加抗VLA-4 mAb治疗的受体小鼠中，Th2细胞因子表达不佳使得Th1细胞因子持续表达。在FK506治疗的小鼠中，Th1和Th2细胞因子表达均受到抑制。得出结论，通过阻断细胞黏附诱导的免疫耐受和延长移植物存活受不同细胞因子表达的调节。
