Adaptive Restoration Of T-Cell Motility By Cold Acclimation Through Metabolic And Transcriptiona

10 Apr 20264 min read0 viewsJournal Feed

GIST

ObjectivesLow temperatures reduce T-cell motility; however, the mechanisms by which T cells adapt to low-temperature environments remain poorly understood. Here, we investigated how T cells respond and adapt to subphysiological temperatures.MethodsConalbumin-specific D10 T cells were analyzed by time-lapse live-cell imaging using an inverted microscope equipped with a temperature-controlled chamber.

Cellular respiration was assessed using a Seahorse XFe96 analyzer, and transcriptomic changes were examined by RNA sequencing.ResultsAt 37°C, T cells exhibited active lamellipodia-driven migration. Reducing the temperature below 32°C progressively suppressed crawling motility, accompanied by increased cell rounding.

At 26°C, motility was markedly reduced in non-acclimated T cells. Unexpectedly, T cells transiently exposed to low temperatures during routine passaging retained motility under cold conditions, suggesting the induction of cold acclimation.

Consistent with this interpretation, T cells cultured at temperatures between 30°C and 26°C for 24 h exhibited enhanced motility when evaluated at the corresponding temperatures compared with non-acclimated cells, with the most pronounced functional difference observed at 26°C. Cold acclimation at 26°C was also associated with a marked increase in mitochondrial spare respiratory capacity.

Clinical Editorial

Summary

Adaptive remodeling of T-cell motility in cold exposure: design, findings, and implications

Study aims and design

The investigation sought to understand how T cells respond and adapt to subphysiological temperatures, focusing on migratory behavior, metabolic state, and transcriptional changes.
Experimental approaches combined time-lapse live-cell imaging in a temperature-controlled chamber, metabolic assessment via Seahorse XFe96, and transcriptomic profiling by RNA sequencing.
The model utilized conalbumin-specific D10 T cells, with assessments across a temperature range including 37°C, 32°C, 30–26°C, and evaluations of acclimation effects.

Temperature effects on motility and morphology

At physiological temperature (37°C), T cells displayed active, lamellipodia-driven crawling.
Reducing temperature below 32°C progressively suppressed migratory activity and promoted cell rounding.
At 26°C, non-acclimated T cells showed markedly reduced motility.

Evidence for cold acclimation and functional restoration

Brief exposure to low temperatures during routine passaging unexpectedly preserved motility when subsequently tested under cold conditions, indicating cold acclimation.
Prolonged culture at 30–26°C for 24 hours enhanced motility at the corresponding temperatures in acclimated versus non-acclimated cells, with the largest effect at 26°C.

Metabolic remodeling accompanying acclimation

Cold acclimation at 26°C coincided with a substantial rise in mitochondrial spare respiratory capacity, suggesting enhanced metabolic flexibility to support motility under cold stress.

Transcriptional reprogramming associated with adaptation

RNA sequencing revealed broad transcriptional shifts after cold acclimation.
Upregulated pathways encompassed ribosome biogenesis, RNA processing, transcriptional regulation, and protein quality control.
Downregulated gene sets included DNA replication, DNA repair, and cell cycle progression, consistent with a shift toward remodeling over proliferation.

Context, limitations, and implications

The study supports a view of temperature as an active regulator of immune cell dynamics, not merely an environmental constraint.
Limitations include reliance on a single T-cell model and in vitro conditions; extrapolation to in vivo physiology requires caution.