Rapid burst of H2O2 by plant growth regulators increases intracellular Ca2+ amounts and modulates CD4+ T cell activation

Ahmed, Asma; Mukherjee, Soham; Deobagkar-Lele, Mukta; Naik, Tikeswar; Nandi, Dipankar

doi:10.1016/j.intimp.2010.08.005

Cited by 4 publications

(1 citation statement)

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“…T cells were seeded at a density of ∼ 50,000 cells/well and activated using two models: (i) PMA (10 ng/mL) and Ionomcyin (0.1 or 0.5 μM) or Thapsigargin (0.01 or 0.05 μM), a TCR-independent activation model, to recapitulate optimal and high calcium levels (13,14) (ii) plate bound anti-mouse CD3 and soluble anti-mouse CD28, a TCR-dependent activation model (8,15). For anti-CD3/anti-CD28 based activation, 96 well U-bottomed plates (Corning, USA) were coated with 0.5 μg/mL of hamster anti-mouse CD3 (eBioscience, USA) and incubated overnight at 4°C (8).…”

Section: Methodsmentioning

confidence: 99%

High intracellular calcium amounts inhibit activation-induced proliferation of mouse T cells

Joseph,

Kumar,

Chatterjee

et al. 2024

Preprint

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Optimal T cell activation is critical to orchestrate adaptive immune responses. Calcium is critical for T cell activation and integrates signaling pathways necessary to activate key transcription factors. In fact, patients with calcium channelopathies are immunodeficient. Here, we investigated the effects of different concentrations of intracellular calcium on activation of mouse T cells. High intracellular calcium amounts inhibitedin vitroT cell proliferation as evidenced by a decreased cell cycling-to-hypodiploidy ratio in two models of activation: the combination of phorbol 12-myristate 13-acetate (PMA) and Ionomycin (an ionophore)/Thapsigargin (a SERCA inhibitor) or plate bound anti-CD3 and anti-CD28. High intracellular calcium amounts increased the production of reactive oxygen species (ROS) in T cells activated with PMA and Ionomycin and scavenging excess ROS using N-acetyl cysteine (NAC) or PEGylated superoxide dismutase (PEG-SOD) rescued the decrease in cycling-to-hypodiploidy ratio. To test the universality of our observations, we studied the effects of tert-Butylhydroquinone (tBHQ), a SERCA inhibitor and Nrf2 activator. tBHQ alone did not increase intracellular calcium amounts but increase was observed along with PMA. Also, tBHQ inhibited T cell activation in a dose-dependent manner in bothin vitromodels of T cell activation. Importantly, intraperitoneal injection of tBHQ ameliorated Dextran Sodium Sulfate (DSS)-induced colitis in mice as evidenced by rescue of colon length shortening and lower disease activity index. Overall, this study identifies high calcium amounts as a potential target to lower T cell activation. The implications of these observations are discussed as this strategy may be important in treatment of some autoimmune diseases.

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