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In Type 1 Diabetes Immunocompetent Cells are Defective in IL‐16 Secretion

To the Editor: Interleukin-16 (IL-16) is a chemo-attractant factor for T cell lymphocytes, including T regulatory cells, which is released by peripheral blood mononuclear cells (PBMC) upon activation [1]. The generation of IL-16 in its active form requires the cleavage of pro-IL-16 by caspase-3, the main executioner of the apoptotic machinery [2]. We and others have previously shown that a defect in caspase-3 expression occurs in peripheral immunocompetent cells of subjects with type 1 diabetes mellitus (T1D) and that this defect is shared with other autoimmune diseases such as chronic autoimmune thyroiditis, autoimmune polyendocrine syndrome-2 and multiple sclerosis [3–5]. Based on these premises, we hypothesized that because an impaired expression of caspase-3 is a common trait in patients with T1D, such individuals will also present defective secretion of IL-16. To this end, sera and PBMC were obtained from a total number of 13 subjects with T1D (26.9 ± 7.6 years old, five women, eight men, disease duration 11 ± 8.0) and 13 healthy subjects (33.5 ± 8.6, seven women and six men). Sera were stored at )80 C until analysed, while PBMC were cultured (1 · 10 ⁄ ml) in RPMI1640 and activated with PHA (Sigma, St Louis, MO, USA) at 5 lg ⁄ ml for 72 h. Supernatants were then collected for IL-16 measurement. IL-16 concentrations in sera and culture supernatants were quantified by ELISA (R & D Systems Inc., Minneapolis, MN, USA). We observed that the two groups did not differ in the mean value of sera IL-16 concentrations. However, analysis of culture supernatants showed that IL-16 concentrations were lower in the cultures obtained from patients with T1D compared to healthy controls (57.57 ± 15.01 versus 84.47 ± 15.92 pg ⁄ ml, P = 0.003 by Mann–Whitney; Fig. 1A). As IL-16 secretion is dependent on caspase-3 activity, we also analysed the intracellular expression of this molecule by flow cytometry using an anti-active-caspase-3 antibody (BD Biosciences, San Diego, CA, USA). Active caspase-3 expression was reduced in activated immunocompetent cells obtained from patients with T1D compared to healthy controls (36.62 ± 18.85 versus 56.59 ± 14.11, P = 0.023 by Mann–Whitney; Fig. 1B), affecting both T