B7-1 AND B7-2 COSTIMULATORY MOLECULES ACTIVATE DIFFERENTIALLY THE TH1/TH2 DEVELOPMENTAL PATHWAYS - APPLICATION TO AUTOIMMUNE-DISEASE THERAPY
B7-1 AND B7-2 COSTIMULATORY MOLECULES ACTIVATE DIFFERENTIALLY THE TH1/TH2 DEVELOPMENTAL PATHWAYS - APPLICATION TO AUTOIMMUNE-DISEASE THERAPY
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DOI：
10.1016/0092-8674(95)90349-6
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发表时间：
1995-03-10
期刊：
影响因子：
64.5
通讯作者：
GLIMCHER, LH
中科院分区：
文献类型：
--
作者：
KUCHROO, VK;DAS, MP;GLIMCHER, LH
CD4辅助性T细胞前体细胞沿两种不同途径（Th1和Th2）成熟。在此我们表明，这两种途径可被两种共刺激分子B7 - 1和B7 - 2差异性激活。利用抗B7抗体，在实验性自身免疫性脑脊髓炎（EAE）中，在体外和体内对这一发育步骤进行了调控。抗B7 - 1降低了疾病的发生率，而抗B7 - 2则增加了疾病的严重程度。两种抗体均不影响总体T细胞的诱导，而是改变了细胞因子谱。在免疫接种时给予抗B7 - 1导致主要产生Th2克隆，其转移既阻止了EAE的诱导，又消除了已发生的疾病。由于同时使用抗IL - 4抗体可阻止疾病的改善，共刺激分子可能直接影响初始细胞因子的分泌。因此，B7 - 1和B7 - 2与共同的反受体CD28和CTLA - 4的相互作用通过影响前体细胞向Th1或Th2谱系的分化，在临床疾病中产生非常不同的结果。
CD4 T helper precursor cells mature along two alternative pathways, Th1 and Th2. Here we show that these pathways are differentially activated by two costimulatory molecules, B7-1 and B7-2. Using anti-B7 antibodies, this developmental step was manipulated both in vitro and in vivo in experimental allergic encephalomyelitis (EAE). Anti-B7-1 reduced the incidence of disease while anti-B7-2 increased disease severity. Neither antibody affected overall T cell induction but rather altered cytokine profile. Administration of anti-B7-1 at immunization resulted in predominant generation of Th2 clones whose transfer both prevented induction of EAE and abrogated established disease. Since cotreatment with anti-IL-4 antibody prevented disease amelioration, costimulatory molecules may directly affect initial cytokine secretion. Thus, interaction of B7-1 and B7-2 with shared counterreceptors CD28 and CTLA-4 results in very different outcomes in clinical disease by influencing commitment of precursors to a Th1 or Th2 lineage.