Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes

Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age.In this study,we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models.Splenocytes,CD4+,and nave CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation（CD28 and p21） and the melatonin receptor（MT1A and MT1B） were assessed.The T cell activationrelated proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels.Our data clearly revealed that CD28,p21,MT1 A,and MT1 B mRNA were highly expressed in the presence of melatonin.Co-culture of CD4+ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA,suggesting induction or maintenance of T lymphocyte responses.We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4+ T lymphocytes,suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells.Taken together,we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.