Key Points: Life span estimates can be sensitive to the duration of stable isotope label administration, explaining discrepancies in the literature. Multiexponential models are needed to obtain reliable leukocyte life span estimates.

In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics.

To the editor: Monocytes originate from the bone marrow (BM), are distributed in the bloodstream, and can differentiate in the tissue into skin macrophages or intestinal dendritic cells (DCs).[1][1] They play an essential role in the defense against pathogens[2][2] and are implicated in a range of

Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor alpha (IL-4Rα), markedly improves disease severity in atopic dermatitis (AD) patients. However, the effect of IL-4Rα blockade on dynamics of circulating skin-homing T-cells, which are crucial players in the pathologic mechanism of AD, has not been studied yet. In addition, it remains unknown whether dupilumab treatment induces long-lasting T- and B-cell polarization. Therefore, we studied the short- and long-term effects of dupilumab treatment on IL-4Rα expression and T-cell cytokine production within total and skin-homing (CLA+/CCR4+) subpopulations in moderate-to-severe AD patients. Dupilumab treatment completely blocked IL-4Rα expression and STAT-6 phosphorylation in CD19+ B-cells and CD4+ T-cells already within two hours of administration and through week 52. Although no change in the proportion of skin-homing T-cell subsets was found, dupilumab treatment significantly decreased the percentage of proliferating (Ki67+) and Th2/Th22 cytokine-producing skin-homing CD4+ T-cells already at week 4. No evidence of general Th-cell skewing following a year of dupilumab treatment was found. In summary, dupilumab treatment rapidly and stably inhibited IL-4Rα, which was accompanied by a strong early functional immunological effect specifically on skin-homing T-cells, without effecting overall Th-cell skewing on the long-term.