T cells from elderly persons respond to neoantigenic stimulation with an unimpaired IL-2 production and an enhanced differentiation into effector cells

Abstract

We analysed the capacity of T cells from young and elderly persons to produce IL-2 and IFN-γ after in vitro stimulation with two neoantigens, namely inactivated rabies virus and recombinant Etr protein of tick-borne encephalitis virus (TBEV). Soluble antigens should per definition primarly stimulate CD4 + naı̈ve T cells. Cytokine production was analysed by ELISPOT technology. T cells from elderly and young donors produced similar amounts of IL-2 after priming with both neoantigens. In contrast, IFN-γ production was induced earlier and at lower antigenic concentrations in T cells from elderly persons than from young controls indicating an enhanced capacity of primed T cells to differentiate into effector cells. In both age groups the response pattern to neoantigenic stimulation was the same whether unfractionated blood mononuclear cells or purified CD4 +CD45RA + T cells with autologous DC as APC were used. The magnitude of the response was, however slightly lower in isolated cells. Autologous DC still induced an MLR in purified CD4 +CD45RA + cells, which was more pronounced in the young than in the elderly group. Our results demonstrate that the ability of CD4 + T cells from elderly persons to respond to neoantigenic stimulation is intact and that their capacity to differentiate into effector cells is even enhanced. This is in good agreement with earlier reports on alterations in the homing receptor pattern of naı̈ve T cells in old age. Rapid generation of effector cells from naı̈ve cells may at least partly counterbalance the decreasing size of the naı̈ve T cell pool in elderly persons.