PD-1/PDL-1 blockage restores functions to exhausted CD8+ T cells. In the literature, I always see that people isolate CD8+ T cells with high-PD-1 expression, characteristic of exhaustion. These isolated cells are cultured in vitro, and have impaired functions, but have improved functions when blockade antibody (anti-PD-1 or anti-PDL-1) is added. My question is: Isolated PD-1 high CD8+ T cells, when cultured in vitro, how do they maintain the exhausted phenotypes given that no PDL-1 ligand is added to the medium? If there is no ligand, PD-1 is not activated, then why the anti-PD-1 or anti-PDL-1 even matter? Thanks a lot.
Xiangnan, the point is that high expression of PD1 or PDL1 is a trangenic model in CD8, so the signal transduction is continuous independently if the ligand or stimuli is present. Therefore if you blockade the signal using antibodies or shRNAs (or microRNAs), you can restore functions. Remember that PD1 is inhibitory as well.
@julio E Valdivia
Thanks for your answer. You mean that PD-1 high CD8+ T cells isolated from HIV-infected patients and cultured in vitro maintain its exhausted status even without ligand binding or just because the ligand is preserved during isolation, i.e, PDL-1 still binds PD-1? Transgenic overexpression of PD-1 alone in CD8+ T cells cultured in vitro does not cause exhaustion, since there is no ligand for it. Thanks.
CD8+T primary culture, no in cell lines. I think this paper could help you out:
T cell exhaustion
E John Wherry
Nature Immunology 12, 492–499 (2011) doi:10.1038/ni.2035
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