In-vitro blockade of the CD4 receptor co-signal in antigen-specific T-cell stimulation cultures induces the outgrowth of potent CD4 independent T-cell effectors
Vatter S, Schmid M, Gebhard C, Mirbeth C, Klobuch S, Rehli M, Herr W, Thomas S (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 454
Pages Range: 80-85
DOI: 10.1016/j.jim.2017.11.006
Abstract
T-cell receptor (TCR) redirected T cells are promising tools for adoptive cancer immunotherapy. Since not only CD8 but also CD4 T cells are key players for efficient antitumor responses, the targeted redirection of both subsets with the same antigen-specific TCR comes more and more into focus. Although rapidly evolving technologies enable the reliable genetic re-programming of T cells, the limited availability of TCRs that induce T-cell activation in both T-cell subsets without CD4/CD8 co-receptor contribution hampers the broad application of this approach. We developed a novel stimulation approach, which drives the activation and proliferation of CD4 T-cell populations capable of inducing effector functions in a CD4-independent manner. Naive-enriched CD4 T cells were stimulated against dendritic cells (DC) expressing allogeneic HLA-DP antigens upon RNA transfection and CD4/HLA interactions were blocked by the addition of CD4 binding antibody. Evolving CD4 T-cell populations were specifically activated independent of the CD4 co-signal and induced strong TCR-mediated IFN-γ secretion as well as cytolysis upon recognition of leukemia cells expressing HLA-DP antigen. Our novel stimulation approach may facilitate the generation of CD4 T cells as source for co-receptor independent TCRs for future immunotherapies.
Involved external institutions
Germany (DE)How to cite
APA:
Vatter, S., Schmid, M., Gebhard, C., Mirbeth, C., Klobuch, S., Rehli, M.,... Thomas, S. (2018). In-vitro blockade of the CD4 receptor co-signal in antigen-specific T-cell stimulation cultures induces the outgrowth of potent CD4 independent T-cell effectors. Journal of Immunological Methods, 454, 80-85. https://doi.org/10.1016/j.jim.2017.11.006
MLA:
Vatter, Sarah, et al. "In-vitro blockade of the CD4 receptor co-signal in antigen-specific T-cell stimulation cultures induces the outgrowth of potent CD4 independent T-cell effectors." Journal of Immunological Methods 454 (2018): 80-85.
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