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bioRxiv · 10.1101/2020.04.09.028019

High glucose attenuates Ca2+ influx in cytotoxic T lymphocytes upon target recognition

Zou, H.·Schwaer, G.·Zhao, R.·Alansary, D.·Yin, D.·Schwarz, E. C.·Niemeyer, B.·Qu, B.
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Abstract

The killing efficiency of cytotoxic T lymphocytes (CTLs) is tightly regulated by intracellular Ca2+ concentration. Glucose is the key energy source for CTLs, lack of which significantly impairs CTL activation, proliferation and effector functions. The impact of high glucose on Ca2+ influx in CTLs remains largely elusive. In this work, we stimulated primary human CD8+ T cells in medium containing either 25 mM (high glucose, HG) or 5.6 mM glucose (normal glucose, NG). We found that store-operated calcium entry (SOCE) induced by thapsigargin (Tg) is elevated in HG-cultured CTLs compared to their counterparts in NG. Unexpectedly, the Ca2+ influx elicited by recognition of target cells is reduced in HG-cultured CTLs. Under HG condition, STIM1 and STIM2, the calcium sensors in the endoplasmic reticulum (ER), were down-regulated; ORAI1, the main structural component of calcium-release activated channels, remained unchanged, whereas ORAI2 and ORAI3 were up-regulated. The fraction of necrosis of HG-cultured CTLs was enhanced after killing without affecting glucose uptake. Thus, our findings reveal that HG has a distinctive impact on Tg-evoked SOCE and target recognition-induced Ca2+ influx in CTLs and causes more CTL death after killing, suggesting a novel regulatory role of high glucose on modulating CTL functions.

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Zou, H., Schwaer, G., Zhao, R., Alansary, D., Yin, D., Schwarz, E. C., Niemeyer, B., Qu, B.. 2020-04-10. High glucose attenuates Ca2+ influx in cytotoxic T lymphocytes upon target recognition. https://doi.org/10.1101/2020.04.09.028019

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