Toungouz M, Denys C H, Andrien M E, de Groote D, Dupont E C
Department of Immunology and Transfusion, Erasme Hospital, University Clinics of Brussels, Belgium.
Transplantation. 1994 Dec 27;58(12):1393-8.
Serologically defined MHC class II differences provoke release of TNF-alpha and IL-6 during MLR. In order to assess the influence of micropolymorphism defined at the genomic level, we selected informative donors pairs within DR2 DR4 serologically defined unrelated subjects by combining those differing only by DR4 alleles, as assessed by PCR-SSOP (DRB1*0401 to 07). Two groups of MLR combinations were tested including DRB1-identical (group 1, n = 12) and one DRB1 difference (group 2, n = 16). Pairs of HLA-identical siblings (n = 4) and of unrelated subjects differing by two major DR incompatibilities detected by serology (n = 27) were used as controls. We further investigated whether DP and DQ differences contributed to the observed CK production. Comparison of group 2 with group 1 showed that one DRB1 difference had a marked influence on CK production at day 3 (TNF-alpha: 401.8 +/- 85 pg/ml vs. 128.7 +/- 34.5 pg/ml, P = 0.001; SI = 2.97 +/- 0.23 vs. 1.27 +/- 0.09, P < 0.0001; IL-6: 317.6 +/- 44.8 pg/ml vs. 108 +/- 13 pg/ml, P = 0.003; SI = 2.53 +/- 0.37 vs. 1.11 +/- 0.05, P < 0.0001). However, CK release in group 2 was significantly lower than that observed in subjects with two serologically defined DR differences (TNF-alpha: 515.1 +/- 61.4 pg/ml, P = 0.05; SI = 5.61 +/- 0.48, P < 0.0001; IL-6: 545.9 +/- 75.8 pg/ml, P = 0.03; SI = 4.75 +/- 0.58, P < 0.0004). Addition of LPS after one day of MLR resulted in discriminant production of CK in group 2 as compared with group 1. Neither DP nor DQ differences affected CK production. In conclusion, DR subtypic differences induce significant CK release during primary MLR. This in vitro study demonstrates the immunodominance of the DR system in eliciting strong inflammatory mediators release.
血清学定义的MHC II类差异在混合淋巴细胞反应（MLR）期间可引发肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的释放。为了评估基因组水平定义的微多态性的影响，我们通过组合那些仅在DR4等位基因上不同的个体（通过PCR-SSOP评估，DRB1*0401至07），在血清学定义的DR2 DR4无关个体中选择了信息丰富的供体对。测试了两组MLR组合，包括DRB1相同的组（第1组，n = 12）和一个DRB1差异的组（第2组，n = 16）。 HLA相同的同胞对（n = 4）和血清学检测到有两个主要DR不相容性差异的无关个体对（n = 27）用作对照。我们进一步研究了DP和DQ差异是否导致观察到的细胞因子（CK）产生。第2组与第1组的比较表明，一个DRB1差异对第3天的CK产生有显著影响（TNF-α：401.8±85 pg/ml对128.7±34.5 pg/ml，P = 0.001；SI = 2.97±0.23对1.27±0.09，P <0.0001；IL-6：317.6±44.8 pg/ml对108±13 pg/ml，P = 0.003；SI = 2.53±0.37对1.11±0.05，P <0.0001）。然而，第2组中的CK释放明显低于血清学定义的两个DR差异的个体中观察到的释放（TNF-α：515.1±61.4 pg/ml，P = 0.05；SI = 5.61±0.48，P <0.0001；IL-6：545.9±75.8 pg/ml，P = 0.03；SI = 4.75±0.58，P <0.0004）。MLR一天后添加脂多糖（LPS）导致第2组与第1组相比有判别性的CK产生。DP和DQ差异均未影响CK产生。总之，DR亚型差异在原发性MLR期间诱导显著的CK释放。这项体外研究证明了DR系统在引发强烈炎症介质释放中的免疫优势。
