Radhakrishnan Suresh, Iijima Koji, Kobayashi Takao, Kita Hirohito, Pease Larry R
Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
J Allergy Clin Immunol. 2005 Sep;116(3):668-74. doi: 10.1016/j.jaci.2005.04.038.
Allergic asthma is an increasing clinical problem that might be addressed with immunologically based interventions. A novel human antibody that activates human and mouse dendritic cells (DCs) by cross-linking B7-DC has strong immunomodulatory properties and blocks antigen-induced inflammatory lung disease in mice.
We sought to evaluate the ability of activated DCs to mediate an antibody-induced protective response against inflammatory lung disease.
An adoptive transfer strategy was used to test the ability of antibody treatments to activate DCs, inducing a protective response against inflammatory lung disease in mice presensitized to ovalbumin (OVA). After transfer of activated DCs, recipient mice were exposed repeatedly to airway antigen and evaluated for changes in immune reactivity and airway inflammatory disease.
Animals presensitized to OVA receiving either systemic treatments with B7-DC cross-linking antibody (XAb) or adoptively transferred antibody-activated DCs were completely protected from airway inflammatory responses normally induced by repeated exposure to OVA. Lymphocytes isolated from spleens or lung-draining lymph nodes of treated animals were highly responsive to OVA and secreted TNF-alpha, IFN-gamma, and IL-10. In contrast, IL-4 was not produced by cells isolated from animals receiving B7-DC XAb.
Activation of DCs with B7-DC XAb ex vivo before adoptive transfer into presensitized mice is sufficient to protect animals completely from inflammatory lung disease induced by subsequent repeated airway exposure to the offending antigen. This finding is consistent with our hypothesis that in vivo administration of B7-DC XAb modulates the immune response by activating endogenous DCs.
过敏性哮喘是一个日益严重的临床问题，可能可通过基于免疫的干预措施来解决。一种通过交联B7-DC激活人和小鼠树突状细胞（DC）的新型人抗体具有强大的免疫调节特性，并可阻断小鼠抗原诱导的炎症性肺病。
我们试图评估活化的DC介导抗体诱导的针对炎症性肺病的保护性反应的能力。
采用过继转移策略来测试抗体治疗激活DC的能力，诱导对卵清蛋白（OVA）致敏小鼠的炎症性肺病产生保护性反应。在转移活化的DC后，受体小鼠反复暴露于气道抗原，并评估免疫反应性和气道炎性疾病的变化。
预先对OVA致敏的动物，接受B7-DC交联抗体（XAb）全身治疗或过继转移抗体活化的DC后，完全免受反复暴露于OVA通常诱导的气道炎症反应。从治疗动物的脾脏或肺引流淋巴结分离的淋巴细胞对OVA高度反应，并分泌肿瘤坏死因子-α、干扰素-γ和白细胞介素-10。相比之下，从接受B7-DC XAb的动物分离的细胞不产生白细胞介素-4。
在过继转移到预先致敏的小鼠体内之前，用B7-DC XAb在体外激活DC足以使动物完全免受随后反复气道暴露于致病抗原所诱导的炎症性肺病。这一发现与我们的假设一致，即体内给予B7-DC XAb通过激活内源性DC来调节免疫反应。
