Systemic administration of cellular interleukin-10 can exacerbate cardiac allograft rejection in mice.
Systemic administration of cellular interleukin-10 can exacerbate cardiac allograft rejection in mice.
复制标题
全身给予细胞白细胞介素 10 会加剧小鼠心脏同种异体移植排斥反应。
DOI：
10.1097/00007890-199612270-00002
复制
发表时间：
1996
期刊：
影响因子：
6.2
通讯作者：
Thomson,AW
中科院分区：
文献类型：
--
作者：
Qian,S;Li,W;Li,Y;Fu,F;Lu,L;Fung,JJ;Thomson,AW
细胞白细胞介素-10（cIL-10）已显示通过阻断抗原呈递细胞功能来抑制1型辅助性T细胞（Th 1）产生细胞因子。这种活性表明IL-10可能在移植排斥的治疗中是有用的。然而，IL-10对T和B细胞分化的刺激作用也被观察到。在这项研究中，我们研究了重组（r）小鼠（m）IL-10对B10（H2 B）→ C3 H（H2 k）品系组合中异位血管化心脏移植物存活的影响，该品系组合跨越主要组织相容性复合体（MHC）和非MHC-组织相容性抗原（non-MHC-HA）屏障。还在B10中检查了IL-10的影响。BR（H2 k）→ C3 H组合，仅在非MHC-HA基因座存在差异。术后腹腔注射IL-10（100 μg/d，第0-6天）可显著加速B10→ C3 H组（平均存活时间[MST] 7.8±0.2天;对照组MST 10.6±0.6天; P< 0.05）和B10 → C3 H组（平均存活时间[MST] 7.8±0.2天; P< 0.05）的心脏移植排斥反应。BR→ C3 H组合（MST 14.3±0.5天;对照MST 77.7±14.4天）。离体IL-10灌注供体心脏15分钟或2小时不影响随后的移植物存活。对移植小鼠的免疫学监测显示，IL-10处理（100 μg/d，ip，第0-6天）增加了循环补体依赖性细胞毒性（CDC）抗体滴度和脾抗供体细胞毒性T淋巴细胞（CTL）活性，直至移植后3周。这些发现表明，移植后全身给予cIL-10可促进血管化同种异体移植物排斥反应，这可能反映了B和T细胞同种免疫应答的刺激。
Cellular interleukin-10 (cIL-10) has been shown to inhibit cytokine production by T helper type 1 (Th1) cells by blocking antigen presenting cell function. This activity has suggested that IL-10 might be useful in the treatment of transplant rejection. Stimulatory effects of IL-10 however, have also been observed both on T and B cell differentiation. In this study, we examined the influence of recombinant (r) mouse (m) IL-10 on heterotopic vascularized heart allograft survival in the B10 (H2 b)→ C3H (H2 k) strain combination that crosses both major histocompatibility complex (MHC) and non-MHC-histocompatibility antigen (non-MHC-HA) barriers. The influence of IL-10 was also examined in the B10. BR (H2 k)→ C3H combination with disparity at only non-MHC-HA loci. Postoperative intraperitoneal administration of IL-10 (100 μg/d, days 0-6) significantly accelerated heart graft rejection both in the B10→ C3H (mean survival time [MST] 7.8±0.2 days; control MST 10.6±0.6 days; P< 0.05) and the B10. BR→ C3H combination (MST 14.3±0.5 days; control MST 77.7±14.4 days). Ex vivo IL-10 perfusion of donor hearts for either 15 min or 2 hr did not affect subsequent graft survival. Immunologic monitoring of transplanted mice revealed that IL-10 treatment (100 μg/d, ip, days 0-6) increased both the circulating complement-dependent cytotoxic (CDC) antibody titer and splenic anti-donor cytotoxic T lymphocyte (CTL) activity measured up to 3 weeks posttransplant. These findings indicate that post transplant systemic administration of cIL-10 can promote vascularized allograft rejection, and that this may reflect stimulation both of B and T cell alloimmune responses.