IL-9-producing Th9 cells display a group of helper T cells with similarities to Th17 and Th2 T cells and have been shown to be involved in synovial inflammation in rheumatoid arthritis (RA) patients. So far, it is unclear which parameters drive Th9 differentiation in lymphocytes derived from RA patients compared to immunologically healthy individuals and whether autocrine mechanisms are able to enhance Th9 polarization. Further, parallel pathways of induction of IL-17-producing cells with Th9 phenotype have to be distinguished from exclusively Th9-inductive mechanisms. Thus, the present study aimed to determine the parameters of Th9 induction by simulation in a standardized inflammatory cytokine milieu.Peripheral naive and non-naive T cells of RA patients and healthy donors (HD) were cultured under Th9 and Th17-driving conditions and phenotypically analyzed by flow cytometry and molecular analysis.Our findings indicate a similar differentiation pathway of Th9 and Th17 cells and similar distributions of IL-9+ T cells in RA and HD regardless of Th9- or Th17-promoting cytokine milieus. Whereas the magnitude and direction of Th9- or Th17-polarization was about the same in RA and HD, IL-17+ CD4+ T cells were significantly stimulated by Th17-inducing conditions in HD. In conclusion, the results indicate that Th9- and Th17-inducing cytokine conditions mimicking autoimmune inflammation in RA may have similar stimulatory effects regarding polarization of peripheral naive and non-naive T cells into Th9 or Th17 cells. The results suggest that the differentiation of Th9 cells may be also induced by Th17-driving conditions.

Primary prevention strategies, such as vaccinations at the age extremes, in neonates and elderly individuals, demonstrate a challenge to health professionals and public health specialists. The aspects of the differentiation and maturation of the adaptive immune system, the functional implications of immunological immaturity or immunosenescence and its impact on vaccine immunogenicity and efficacy will be highlighted in this review. Several approaches have been undertaken to promote Th1 responses in neonates and to enhance immune functions in elderly, such as conjugation to carrier proteins, addition of adjuvants, concomitant vaccination with other vaccines, change in antigen concentrations or dose intervals or use of different administration routes. Also, early protection by maternal vaccination seems to be beneficial in neonates. However, it also appears necessary to think of other end points than antibody concentrations to assess vaccine efficacy in neonates or elderly, as also the cellular immune response may be impaired by the mechanisms of immaturity, underlying health conditions, immunosuppressive treatments or immunosenescence. Thus, lifespan vaccine programs should be implemented to all individuals on a population level not only to improve herd protection and to maintain protective antibody levels and immune memory, but also to cover all age groups, to protect unvaccinated elderly persons and to provide indirect protection for neonates and small infants.

Introduction Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months. Case presentation Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry. T cell receptor excision circles and relative telomere length quantification were performed on deoxyribonucleic acid isolated from naive (CD4+CD28+CD45RA+) T cells and investigated via reverse transcription polymerase chain reaction. Ki67 expression was studied by immunohistochemistry on naive T cells. The non-parametric Mann-Whitney U test and Wilcoxon test for two independent groups of variables were used to compare healthy donors with patients with juvenile idiopathic arthritis. During follow-up, patients with juvenile idiopathic arthritis showed lower total counts of naive and CD28-expressing T cells compared to healthy donors. Acute exacerbation led to low naive and CD28+ T cell populations and elevated proportions of Ki67-expressing CD4+ naive T cells. In conditions of exacerbation, T cell receptor excision circle numbers were in the lower range in patients with juvenile idiopathic arthritis and increased after follow-up. Healthy donors showed significantly higher relative telomere lengths compared to patients with juvenile idiopathic arthritis. Conclusions This investigation illustrates that the changes in T cell homeostasis in patients with juvenile idiopathic arthritis may be the result of several mechanisms, such as diminished thymus function and peripheral exertions to maintain the peripheral T cell pool. The results also demonstrate that hallmarks of immunosenescence such as decreased naive T cell levels and lower T cell receptor excision circle numbers can only be interpreted together with replication markers such as relative telomere length or Ki67 expression.

Background Significant immunomodulatory effects have been described as result of cigarette smoking in adults and pregnant women. However, the effect of cigarette smoking during pregnancy on the lymphocyte subpopulations in newborns has been discussed, controversially. Methods In a prospective birth cohort, we analyzed the peripheral lymphocyte subpopulations of smoking (SM) and non-smoking mothers (NSM) and their newborns and the replicative history of neonatal, mostly naive CD4 + CD45RA + T cells by measurements of T-cell-receptor-excision-circles (TRECs), relative telomere lengths (RTL) and the serum cytokine concentrations. Results SM had higher lymphocyte counts than NSM. Comparing SM and NSM and SM newborns with NSM newborns, no significant differences in proportions of lymphocyte subpopulations were seen. Regardless of their smoking habits, mothers had significantly lower naive T cells and higher memory and effector T cells than newborns. NSM had significantly lower percentages of CD4 + CD25++ T cells compared to their newborns, which was not significant in SM. There were no differences regarding cytokine concentrations in newborns of SM and NSM. However, NSM had significantly higher Interleukin-7 concentrations than their newborns. Regardless of smoking habits of mothers, newborns had significantly longer telomeres and higher TRECs than their mothers. Newborns of SM had significantly longer telomeres than newborns of NSM. Conclusions Apart from higher lymphocyte counts in SM, our results did not reveal differences between lymphocyte subpopulations of SM and NSM and their newborns, respectively. Our finding of significantly longer RTL in newborns of SM may reflect potential harm on lymphocytes, such as cytogenetic damage induced by smoking.

Background The aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI). Methods The retrospective evaluation (2002–2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002–2005) was compared with the recommended and early funded (2006–2007) and the funded (2008–2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons. Results In 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0–11 months (by 87.8%), 6–10 years (by 84.2%) and 11–18 years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0–11 months. Conclusions UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE.