Group I mGlu receptor stimulation inhibits activation‐induced cell death of human T lymphocytes

1 The effects of L ‐glutamate on activation‐induced cell death (AICD) of human activated (1  μ g ml −1 phytohemagglutinin plus 2 U ml −1 interleukin‐2; 8 days) T lymphocytes were studied by measuring anti‐CD3 monoclonal antibody (10  μ g ml −1 ; 18 h)‐induced cell apoptosis (Annexin V and propidium iodide staining). 2 L ‐Glutamate (1 × 10 −8 –1 × 10 −4   M ) significantly ( P 0.01) inhibited AICD in a concentration‐dependent manner (EC 50 =6.3 × 10 −8   M ; maximum inhibition 54.8±6.3% at 1 × 10 −6   M ). 3 The L ‐glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC 50 values were: 3.2 × 10 −7   M for (1 S ,3 R )‐ACPD; 4.5 × 10 −8   M for quisqualate; 1.0 × 10 −6   M for ( S )‐3,5‐DHPG; 2.0 × 10 −5   M for CHPG. 4 Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10 −6   M . The IC 50 values calculated were: 8.7 × 10 −5 , 4.3 × 10 −6 and 6.3 × 10 −7   M for AIDA, LY 367385 and MPEP, respectively. 5 L ‐Glutamate (1 × 10 −6 M; 18 h) significantly ( P 0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. 6 Expression of both mGlu 1 and mGlu 5 receptor mRNA by T lymphocytes and T‐cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests that L ‐glutamate‐mediated inhibition of AICD was exerted on T cells. 7 These data depict a novel role for L ‐glutamate in the regulation of the immune response through group I mGlu receptor‐mediated mechanisms.British Journal of Pharmacology (2006) 148 , 760–768. doi: 10.1038/sj.bjp.0706746