Exercise Affects T-Cell Function by Modifying Intracellular Calcium Homeostasis.

Purpose: The study aimed to investigate the effects of chronic moderate exercise on regulation of intracellular calcium signaling as an important link to proliferation capacity in murine splenic T lymphocytes.

Methods: Male CD1 Swiss mice were randomly assigned either to a control group (CG) or an exercise training group (EG). EG mice performed voluntary exercise for 3 months. Lymphocytes were isolated from murine spleens and intracellular calcium was determined by using Fura-2(AM) and fluorescence spectrometry. The combination of flow cytometry and carboxy-fluorescein succinimidyl ester labeling technique was used for determination of cell proliferation. The expression levels of Ca-regulating genes were determined by quantitative polymerase chain reaction (qPCR) analysis.

Results: Basal [Ca]i was significantly higher in mice from the EG compared with mice of the CG (P < 0.001, n = 6). Similarly, [Ca]i transients after stimulation with phytohemagglutinin, concanavalin A, and the anti-CD3 antibody induced were significantly increased in mice from the EG (P < 0.05, n = 5). However, no differences were found after stimulation with thapsigargin (P < 0.05, n = 5). CD3 T cells from EG showed higher mitogen-induced proliferation levels than from CG (P < 0.05/0.01, n = 5). The mRNA expression of cellular Ca-regulating genes, such as STIM1, Cav2.3, TRPV4, IP3R2, ORAI1, MCU, TRPM5, and TRPC1, were significantly downregulated (P < 0.05/0.01, n = 5).

Conclusion: This study suggests that chronic moderate exercise improves intracellular Ca signaling in murine splenic lymphocytes. The enhanced availability of the second messenger Ca is followed by an improved cellular function such as cell proliferation. The downregulation of Ca homeostasis-related factor expression might be considered as a self-protective mechanism against elevated intracellular Ca signals.