Establishment of HIV-specific cytotoxic T cells via TCR gene cloning and gene transfer using in vivo information

点击翻译按钮获取中文摘要

HIV-specific cytotoxic T cells have been regarded to be an important factor to control HIV infection. However, in the patients infected with HIV, T cell antigen receptor zeta chain down-regulation and impaired in vitro T cell function have been described. This phenomenon could potentially make the development of HIV-specific vaccination difficult. We, therefore, tried to establish alternative HIV-specific immunotherapy.At present, we do not have a sufficient range of strategies for manipulating antigen-specific T cells. We propose that T cell receptor gene transfer could be used for antigen-specific immunotherapy. In the proposed technique, important antigen-specific T cells in patients would first be identified, and then a pair of cDNAs encoding alpha and beta T cell receptors would be isolated from these single T cells. These genes would then be transferred into self lymphocytes. These engineered antigen-specific cells also manipulated to express appropriate functional genes could then be applied to specific immunotherapy.In order to prove this system can work in HIV infection, we used an experimental system, in which immune responses against HIV env gp160 pepetide P18IIIB was elicited in BALB/c mice. We demonstrated that HIV specific CTL could be obtained using TCR gene cloning using the information of TCR clonal analysis and reconstitution of the TCR function by gene transfer.