Inflammation and immunological dysfunction by HTLV-1 bZIP factor in HTLV-1 associated dieases

HTLV-1 bZIP因子（HBZ）由HTLV-1原病毒负链编码，在所有ATL病例和HTLV-1携带者中均有表达。HBZ转基因小鼠不仅会发生T细胞淋巴瘤，还会发生炎症性疾病。我们发现干扰素-γ (IFN-γ)的过量产生引起了这些炎症。作为一种机制，HBZ诱导的Foxp3表达是不稳定的，它将Foxp3+ T细胞转化为IFN-γ过量产生的Foxp3 - T细胞。HTLV -1感染者的细胞介导免疫功能受损。作为这种免疫缺陷的机制，我们发现HBZ抑制NFAT和AP-1，从而抑制CD4+ T细胞中IFN-γ的产生。

HTLV -1 bZIP factor (HBZ) is encoded by the minus strand of HTLV -1 provirus, and expressed in all ATL cases and HTLV-1 carriers. HBZ transgenic mice develop not only T -cell lymphomas but also inflammatory diseases. We found that overproduction of interferon-γ (IFN-γ) caused these inflammation. As a mechanism, Foxp3 expression that is induced by HBZ is unstable, which converts Foxp3+ T cells to Foxp3 - T cells with IFN-γ overproduction. HTLV -1 infected individuals have impaired cell-mediated immunity. As a mechanism of this immunodeficiency, we found that HBZ inhibited NFAT and AP-1, which leads to suppressed production of IFN-γ in CD4+ T cells.