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携带者中表达。HBZ转基因小鼠不仅发生T细胞淋巴瘤，而且发生炎性疾病。我们发现，过量产生的干扰素-γ（IFN-γ）引起这些炎症。作为一种机制，由HBZ诱导的Foxp 3表达是不稳定的，其将Foxp 3 + T细胞转化为具有IFN-γ过量产生的Foxp 3- T细胞。HTLV-1感染的个体具有受损的细胞介导的免疫。作为这种免疫缺陷的机制，我们发现HBZ抑制NFAT和AP-1，这导致抑制CD 4 + 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.