Specific adoptive immunotherapy of malignant glioma with long-term cytotoxic T lymphocyte line expanded in T-cell growth factor

Abstract

The purposes of the current study were: (1) to investigate the immunoregulatory effects of T-cell growth factor (TCGF) on the activation and differentiation of syngeneic cytotoxic T lymphocyte (CTL) populations generated against a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma, in C57BL/6 mice; and (2) to determine whether the glioma-specific CTL clone (G-CTLL) could be established by TCGF, and whether the in vivo efficacy of the cloned cells could be rendered more effective in adoptive therapy. It was found that TCGF largely allows the CTL populations to proliferate and thus can activate the depressed cytotoxic activity in tumour-bearing mice. Two lines of G-CTLL were successfully obtained by the limiting dilution technique. The G-CTLL retained a TCGF-dependent proliferative growth and a marked cytotoxic activity with target specificity for over 18 months, characterized by a surface phenotype of Lyt-1-.2.3+, Lyt-2 antibody blocking of cytotoxicity and the production of immune interferon in response to mitogen and tumour antigen. In the Winn assay and the adoptive transfer assay, the therapeutic effects were detected in intracranially inoculated tumours in mice. The in vivo efficacy was dependent on the dose of G-CTLL and on the time of the intravenous administration, although the transfer was inversely ineffective in conditions of increased intracranial pressure. The mechanism responsible for the in vivo effect was probably due to the adoptive immunity and/or the tumour-specific interferon production of G-CTLL.

Upregulation of indoleamine 2,3‐dioxygenase in hepatocyte during acute hepatitis caused by hepatitis B virus‐specific cytotoxic T lymphocytes in vivo

“…As shown in Figure 5, the IDO expression in primary hepatocytes was induced by murine recombinant IFN‐γ in vitro . In this acute hepatitis model, a large amount of IFN‐γ is produced by HBV‐specific CTL that directly contact HBsAg‐positive hepatocytes (4, 24). Moreover, IFN‐γ mRNA expression was upregulated at least 3–5 days after CTL injection in this murine acute hepatitis model (25).…”