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INTRODUCTION: The aim of the study was to describe the interrelationship between senescence, depression, and immunity. METHODS: We assessed 10 elderly patients with depression and 10 age- and sex-matched controls: before, at one and at six month intervals after the anti-influenza vaccination. Levels of TNFalpha, IL6, ACTH, and cortisol, titres of anti-hemagglutinins and anti-neuraminidases, lymphocytes secreting IFNgamma, IL2, IL4, and IL10, cytotoxicity of NK and CD3+ CD8+ IFNgamma+ cells, anti-CMV antibodies, and CD28- CD57+ lymphocytes known to be associated with the CMV carrier status were evaluated. RESULTS: Higher levels of anti-CMV, higher percentage of the CD28- CD57+ cells, and elevated levels of TNFalpha, IL6, and cortisol concomitant with decreased levels of ACTH and insufficient production of IL10 (which increased the IFNgamma+ /IL10+ ratio) were found in the patients suffering from depression, in comparison to healthy controls. The subjects with depression revealed a low NK cytotoxicity, while a level of CD3+ CD8+ IFNgamma+ cells was comparable between the groups. Although the levels of anti-hemagglutinins and anti-neuraminidases were low in the depressed patients, they reached the protective titres. The majority of these differences disappeared when CMV titres were entered into the analyses as a covariate. DISCUSSION: The results suggest that the elderly depressed patients were characterised by increased exposure to CMV in the past, which could have resulted in a pro-inflammatory profile demonstrated as elevated levels of TNFalpha, IL6 and deficiency of suppressive IL10+ cells. These changes negatively affect humoral and innate response in the depressed patients.

Background Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. Methods The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 106/kg b.w. of autologous expanded CD3+CD4+CD25highCD127− Tregs. Results The disease progressed and all patients were insulin-dependent 2 years after inclusion. The β-cell function measured by c-peptide levels and the use of insulin were the best preserved in patients treated with two doses of Tregs (3/6 in remission), less so after one dose (1/6 in remission) and the worst in untreated controls (no remissions). Increased levels of Tregs could be seen in peripheral blood after their adoptive transfer together with the shift from naïve CD62L+CD45RA+ to memory CD62L+CD45RA− Tregs. Increasing serum levels of proinflammatory cytokines were found: IL6 increased in all subjects, while IL1 and TNFα increased only in untreated group. Therapeutic Tregs were dependent on IL2, and their survival could be improved by other lymphocytes. Conclusions The disease progression was associated with changing proportions of naïve and memory Tregs and slowly increasing proinflammatory activity, which was only partially controlled by the administered Tregs. The therapeutic cells were highly dependent on IL2. We conclude that the therapy should be administered at the earliest to protect the highest possible mass of islets and also to utilize the preserved content of Tregs in the earlier phases of T1DM. Trial registrationhttp://www.controlled-trials.com/ISRCTN06128462; registered retrospectively