Fig. 9.

Age-dependent and age-independent differentiation of regulatory T cells (Tregs)/responder T cells (Tresps) in healthy volunteers and SLE patients. The figure summarizes our findings concerning the age-dependent (a and b) and age-independent (c and d) differentiation of recent thymic emigrant (RTE) Tregs (a and c) or RTE Tresps (b and d) via mature naive (MN) Tregs/Tresps or CD31⁺ memory Tregs/Tresps into CD31⁻ memory Tregs/Tresps for healthy controls (black arrows) and SLE patients (red arrows). An age-dependent increased differentiation of RTE Tregs via CD31⁺ memory Tregs into CD31⁻ memory Tregs, as well as an age-dependent increased conversion of resting naive MN Tregs into CD31⁻ memory Tregs, was found for both healthy controls and SLE patients (a, illustrated by red and black bold arrows). In contrast, with increasing age, an opposite differentiation was found for RTE Tresps, which differentiated increasingly via MN Tresp into CD31⁻ memory Tresps in healthy controls, while those of SLE patients differentiated via CD31⁺ memory Tresps into CD31⁻ memory Tresps (b, illustrated by black and red bold arrows). An age-dependent increased differentiation of resting naive MN Tresps into CD31⁻ memory Tresps was not found for healthy controls or for SLE patients (b). Regarding the age-independent differentiation, our findings show an increased differentiation of RTE Tregs/Tresps via CD31⁺ memory Tregs/Tresps into CD31⁻ memory Tregs/Tresps in SLE patients compared with healthy controls (c and d, illustrated by red bold arrows). Additionally, we found an age-independent increased conversion of resting naive MN Tresps into CD31⁻ memory Tresps in SLE patients compared with healthy controls (d, illustrated by a red bold arrow). These mechanisms may lead to an imbalance between Tregs and Tresps in favor of Tregs (e), especially when the pool of these resting naive MN Tresps is no longer filled up