CTLA-4: a negative regulator of autoimmune disease.
CTLA-4: a negative regulator of autoimmune disease.
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DOI：
10.1084/jem.184.2.783
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发表时间：
1996-08-01
期刊：
影响因子：
--
通讯作者：
Bluestone JA
中科院分区：
文献类型：
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作者：
Karandikar NJ;Vanderlugt CL;Walunas TL;Miller SD;Bluestone JA
CTLA-4是在活化的T细胞上表达的CD 28同源物，以高亲和力结合CD 28配体B7-1（CD 80）和B7-2（CD 86）。本研究旨在研究CTLA-4在调节自身免疫性疾病中的作用。鼠复发-缓解型实验性自身免疫性脑脊髓炎（R-EAE）是SJL/J小鼠中由PLP 139 - 151特异性CD 4 + T细胞介导的脱髓鞘疾病。抗CTLA-4 mAb（或其F（ab）片段）增强PLP 139 -151致敏淋巴结细胞的体外增殖和促炎细胞因子产生。在体外活化培养物中加入任何一种试剂都能增强T细胞过继性转移疾病给幼稚受体的能力。向PLP 139 -151特异性T细胞的接受者体内施用抗CTLA-4 mAb导致疾病加速和恶化。最后，在疾病缓解期间对小鼠的抗CTLA-4治疗导致复发的恶化。总的来说，这些结果表明，CTLA- 4介导正在进行的免疫应答的下调，并在调节自身免疫中发挥重要作用。
CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139- 151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti- CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA- 4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.