Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34+ hematopoietic cells

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

“…29,30 Evidences also suggest immune rejection of transplanted eGFP-positive cells in non-human primate recipients in myeloablative 27 as well as nonablative settings. 28 Hence, using eGFP as a model antigen, herein we show that Lenti-eGFP-transduced DC could effectively process and present the eGFP-derived antigenic peptides to contaminating lymphocytes in DC culture and reproducibly generate CTLs capable of eliminating the eGFP-expressing DCs. These studies provide direct evidence on the efficiency of genetically engineered DCs in inducing antigen-specific immune responses and demonstrate the impact of lymphocyte contamination on genetically modified DCs expressing immunogenic proteins.…”

“…Both CD4 + and CD8 + T-cell-mediated killing of cognate APC populations including DCs, B cells, and macrophages has been reported in several studies [20][21][22][23][43][44][45] and was shown to be mediated via Fas ligand (FasL)-dependent 20,[46][47][48] or -independent mechanisms. 23,44 Similarly, CD8 + CTL-mediated elimination of transplanted neo-antigen-positive T cells and other hematopoietic cells has been previously demonstrated in vivo both in animal models [27][28][29] and humans. 49 In vitro killing of target cells by CD8 + CTLs is mediated primarily by the perforin pathway and to a lesser extent via FasL/Fas interactions, whereas CD4 + T-cell cytotoxicity is conducted essentially by the Fas pathway.…”

“…Supporting our data, previously it has been shown that peptides derived from eGFP degradation are immunogenic in rodents, non-human primates, and humans. [26][27][28][29][30] As a consequence, survival of eGFP gene-modified cells was reduced or completely abrogated in transplanted animals. [27][28][29][30] Furthermore, similar to our findings, other reports suggest that immunostimulatory properties of DCs are linked to their maturation state.…”

“…[26][27][28][29][30] As a consequence, survival of eGFP gene-modified cells was reduced or completely abrogated in transplanted animals. [27][28][29][30] Furthermore, similar to our findings, other reports suggest that immunostimulatory properties of DCs are linked to their maturation state. Systemic expression of antigens on nonprofessional or immature DCs render naïve T cells unresponsive, whereas T-cell responses are rapidly promoted when antigen is presented by mature DCs or in an environment that leads to the activation of DCs.…”

“…We transduced them with a HIV-1-based self-inactivating (SIN) lentiviral vector expressing a widely used reporter molecule, the enhanced green fluorescent protein (eGFP). Previously, it has been shown that eGFP is immunogenic in human, 26 non-human primates 27,28 and in murine models. 29,30 Evidences also suggest immune rejection of transplanted eGFP-positive cells in non-human primate recipients in myeloablative 27 as well as nonablative settings.…”