Khoury S J, Akalin E, Chandraker A, Turka L A, Linsley P S, Sayegh M H, Hancock W W
Multiple Sclerosis Unit, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 1995 Nov 15;155(10):4521-4.
We studied the contribution of the CD28-B7 costimulatory T cell activation pathway to the pathogenesis of experimental autoimmune encephalomyelitis in the Lewis rat model. Systemic administration of CTLA4Ig suppressed clinical disease and was effective even when CTLA4Ig was delayed until day 10 postimmunization, a time when pathologic disease is evident. This protection was not reversible by systemic administration of high doses of IL-2. Detailed immunohistologic studies showed that CTLA4Ig therapy resulted in suppression of the inflammatory response with inhibition of Th1 (IL-2 and IFN-gamma) and sparing of Th2 (IL-4, IL-10, and IL-13) cytokines in the central nervous system. These results indicate that the CD28-B7 T cell costimulatory pathway plays an important role in experimental autoimmune encephalomyelitis, a Th1-mediated disease, and suggest that blockade of this costimulatory pathway protects against active disease by causing a state of immune deviation towards Th2 function. The ability of CTLA4Ig to treat animals with pathologically established disease may have important clinical implications for patients with multiple sclerosis.
我们研究了CD28 - B7共刺激T细胞活化途径在Lewis大鼠模型实验性自身免疫性脑脊髓炎发病机制中的作用。全身给予CTLA4Ig可抑制临床疾病，即使将CTLA4Ig延迟至免疫后第10天给予也有效，此时病理疾病已很明显。高剂量IL - 2全身给药并不能逆转这种保护作用。详细的免疫组织学研究表明，CTLA4Ig治疗可抑制中枢神经系统中的炎症反应，抑制Th1（IL - 2和IFN - γ）细胞因子，而保留Th2（IL - 4、IL - 10和IL - 13）细胞因子。这些结果表明，CD28 - B7 T细胞共刺激途径在实验性自身免疫性脑脊髓炎（一种Th1介导的疾病）中起重要作用，并提示阻断该共刺激途径可通过诱导免疫偏向Th2功能状态来预防活动性疾病。CTLA4Ig治疗已出现病理疾病动物的能力可能对多发性硬化症患者具有重要的临床意义。
