NKT-like (CD3 + CD56+) cells differ from T cells in expression level of cellular protective proteins and sensitivity to stimulation in the process of ageing

BACKGROUND: NKT-like cells are T lymphocytes coexpressing several NK cell-associated receptors. They are effector lymphocytes of innate and adaptive immunity, and their number increases with age. The study aimed to analyze the expression of cellular protective proteins, i.e. sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like and T cells of the young (‘young’, 31 subjects, age range 19–24 years), seniors aged under 85 (‘old’; 30 subjects, age range 65–84 years) and seniors aged over 85 (‘oldest’, 24 subjects, age range 85–94 years). Both NKT-like and T cells were cultured for 48 h and stimulated with IL-2, LPS and PMA with ionomycin and compared with unstimulated control cells. RESULTS: The oldest seniors varied from the other age groups by significantly increased expression of SIRT1 and HSP70 in both NKT-like and T cells observed in both stimulated and nonstimulated cells. The analyzed lymphocyte populations of the oldest revealed not only the highest expression of these proteins but also insensitivity to all types of applied stimulation. When NKT-like cells were compared to T cells, higher expression of the studied protective proteins was observed in both stimulated and unstimulated NKT-like cells. Neither CD3 + CD56+ nor CD3+ cells revealed elevated expression of SOD2, and these cells responded to stimulation until very advanced age. T cells revealed higher sensitivity to stimulation with IL-2 regarding SIRT1 and HSP70 expression. NKT-like cells were more sensitive to stimulation with PMA and ionomycin concerning the expression of these proteins. IL-2 did not induce a significant increase in SOD2 expression in the studied age groups. CONCLUSIONS: The oldest seniors developed an adaptive stress response in both T and NKT-like cells regarding the expression of SIRT1 and HSP70, which was increased and insensitive to further stimulation in contrast to SOD2, which showed a more inducible pattern of expression. CD3 + CD56+ cells exhibited higher expression of cellular protective proteins than CD3+ cells in both stimulated and control, nonstimulated cells. NKT-like and T cells showed a distinct sensitivity to the applied stimulatory factors in the respective age groups.