Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis
Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis
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DOI：
10.1093/intimm/dxh063
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Srivastava, P
中科院分区：
文献类型：
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作者：
Chandawarkar, RY;Wagh, MS;Srivastava, P
使用热休克蛋白 (HSP) gp96 进行免疫可引发针对其来源的癌症或病毒感染细胞的保护性免疫力。低剂量的 gp96 会产生免疫力，而免疫剂量 10 倍的剂量则不会。我们在此表明，注射高剂量的 gp96 会产生 CD4(+) T 细胞，从而下调多种正在进行的免疫反应。高剂量 gp96 免疫可预防 SJL 小鼠髓磷脂碱性蛋白或蛋白脂质蛋白诱导的自身免疫性脑脊髓炎以及非肥胖糖尿病小鼠的糖尿病发作。免疫反应的抑制可以通过CD4(+)细胞过继转移，并且不与CD25表型分开。 gp96（以及可能的其他 HSP）的免疫调节特性可用于抗原特异性激活或抑制细胞免疫反应。后者可能构成自身免疫性疾病新型免疫疗法的基础。
Immunization with heat-shock protein (HSP) gp96 elicits protective immunity to the cancer or virus-infected cells from which it is derived. Low doses of gp96 generate immunity, while doses 10 times the immunizing dose do not. We show here that injection of high doses of gp96 generates CD4(+) T cells that down-regulate a variety of ongoing immune responses. Immunization with high doses of gp96 prevents myelin basic protein- or proteolipid protein-induced autoimmune encephalomyelitis in SJL mice and the onset of diabetes in non-obese diabetic mice. The suppression of immune response can be adoptively transferred with CD4(+) cells and does not partition with the CD25 phenotype. The immunomodulatory properties of gp96 (and possibly other HSP) may be used for antigen-specific activation or suppression of cellular immune responses. The latter may form the basis for novel immunotherapies for autoimmune diseases.