Ex vivo restimulation of human PBMC expands a CD3+CD4-CD8- γδ+ T cell population that can confound the evaluation of CD4 and CD8 T cell responses to vaccination.

The measurement of vaccine-induced humoral and CD4(+) and CD8(+) cellular immune responses represents an important correlate of vaccine efficacy. Accurate and reliable assays evaluating such responses are therefore critical during the clinical development phase of vaccines. T cells play a pivotal role both in coordinating the adaptive and innate immune responses and as effectors. During the assessment of cell-mediated immunity (CMI) in subjects participating in a large-scale influenza vaccine trial, we identified the expansion of an IFN-γ-producing CD3(+)CD4(-)CD8(-) γδ (+) T cell population in the peripheral blood of 90/610 (15%) healthy subjects. The appearance of CD3(+)CD4(-)CD8(-) γδ (+) T cells in the blood of subjects was transient and found to be independent of the study cohort, vaccine group, subject gender and ethnicity, and ex vivo restimulation conditions. Although the function of this population and relevance to vaccination are unclear, their inclusion in the total vaccine-specific T-cell response has the potential to confound data interpretation. It is thus recommended that when evaluating the induction of IFN-γ-producing CD4(+) and CD8(+) immune responses following vaccination, the CD3(+)CD4(-)CD8(-) γδ (+) T cells are either excluded or separately enumerated from the overall frequency determination.

[Sleep disorders, risk of accidents and traffic accidents in a group of drivers of public transport]. / Disturbi del sonno, rischio infortunistico e incidenti stradali in un gruppo di autisti di mezzi pubblici.

In order to evaluate the prevalence of sleep disorders and visuomotor performance, a survey was conducted on 253 drivers of public transport company, aged between 25 and 64 years. Biometric data (BMI, neck circumference and waist, PA) were collected and three questionnaires were administered to investigate sleep disorders. Simple and multiple choice reaction times were administered using a computerized test battery. Records on road accidents in the period 2005-2011 and all accidents in the period 2002-2010 were analyzed. On the basis of clinical and anamnestic questionnaire, workers were divided into two groups: 194 drivers (group 1) without suspicion of sleep disorders and 59 drivers (group 2) with suspected sleep disorders, and 41 with suspected obstructive sleep apnea syndrome (OSAS). The drivers with suspicion of sleep disorders, in particular those with suspected diagnosis of OSAS, showed reaction times significantly prolonged as compared to the drivers of the group 1. In group 2, a higher incidence of (all) accidents was found, whereas the incidence of road accidents was significantly increased only in drivers with suspected OSAS. In addition to the sleep disorders, the use of drugs altering vigilance (antihistamines and benzodiazepines) were significant determinants. In-depth clinical examinations are in progress to confirm the suspected diagnosis of sleep disorders.

Characterization of the human T cell response to rye grass pollen allergens Lol p 1 and Lol p 5.

BACKGROUND: Knowledge of dominant T cell epitopes of major allergens recognized by allergic individuals is required to improve efficacy and safety of allergen immunotherapy. Rye grass pollen (RGP) is the most important source of seasonal aeroallergens in temperate climates and Lol p 1 and Lol p 5 are the two major IgE-reactive allergens. This study aimed to characterize the T cell response to these allergens using a large panel of RGP-sensitive individuals. METHODS: Short-term RGP-specific T cell lines (TCL) were generated from 38 RGP-sensitive subjects and stimulated with Lol p 1 and/or Lol p 5 allergens and synthetic 20-mer peptides. Proliferative responses were determined by 3H-thymidine uptake and IL-5 and IFN-gamma in culture supernatants analysed by ELISA. RESULTS: Of 17 subjects tested for reactivity to both allergens 16 (94%) responded to Lol p 1 and/or Lol p 5, establishing these as major T cell-reactive allergens. Sites of T cell reactivity were spread throughout the allergen molecules but regions of high reactivity were found. For Lol p 1 these spanned residues 19-38, 109-128, 154-173, 190-209, and for Lol p 5 37-56, 100-119, 145-164, 154-173, 190-209, 217-236 and 226-245. IL-5 and IFN-gamma were produced by T cells cultured with proliferation-inducing peptides. CONCLUSIONS: T cell responses to RGP major allergens have been extensively characterized, providing fundamental information for developing T cell-targeted immunotherapy for RGP allergy.