Immunodominance in Mouse and Human CD4+ T-Cell Responses Specific for the Bordetella pertussis Virulence Factor P.69 Pertactin

P.69 pertactin (P.69 Prn), an adhesion molecule from the causative agent of pertussis, Bordetella pertussis, is present in cellular and most acellular vaccines that are currently used worldwide. Although both humoral immunity and cellular immunity directed against P.69 Prn have been implicated in protective immune mechanisms, the identities of CD4⁺ T-cell epitopes on the P.69 Prn protein remain unknown. Here, a single I-A^d-restricted B. pertussis conserved CD4⁺ T-cell epitope at the N terminus of P.69 Prn was identified by using a BALB/c T-cell hybridoma. The epitope appeared immunodominant among four other minor strain-conserved P.69 Prn epitopes recognized after vaccination and B. pertussis infection, and it was capable of evoking a Th1/Th17-type cytokine response. B. pertussis P.69 Prn immune splenocytes did not cross-react with natural variants of the epitope as present in Bordetella parapertussis and Bordetella bronchiseptica. Finally, it was found that the immunodominant P.69 Prn epitope is broadly recognized in the human population by CD4⁺ T cells in an HLA-DQ-restricted manner. During B. pertussis infection, the epitope was associated with a Th1-type CD4⁺ T-cell response. Hence, this novel P.69 Prn epitope is involved in CD4⁺ T-cell immunity after B. pertussis vaccination and infection in mice and, more importantly, in humans. Thus, it may provide a useful tool for the evaluation of the type, magnitude, and maintenance of B. pertussis-specific CD4⁺ T-cell mechanisms in preclinical and clinical vaccine studies.     

Comprehensive cognitive neurological assessment in stroke

Background – Cognitive syndromes (CS) after stroke may be important to measure and monitor for management and emerging therapies. Aim – To incorporate known behavioral neurological and neuropsychiatric syndromes into a bedside cognitive assessment in patients with stroke. Methods – A validated cognitive examination (comprehensive cognitive neurological test in stroke, Coconuts) was administered during the first month of stroke presentation and analyzed according to five large‐scale networks for cognition and correlated with neuropsychological tests. Validity testing of the test was performed for overall sensitivity, specificity, positive predictive value and negative predictive value to stroke in comparison with MRI diagnosis of stroke as well as discriminant validity, construct validity and inter‐rater reliability. Results – Overall the sensitivity of the Coconuts scale was 91% and specificity 35%, PPV 88% and NPV 41% vs stroke lesions using MRI. Cognitive syndrome frequencies: frontal network syndrome frequency was 908/1796 (51%), left hemisphere network syndrome frequency was 646/1796 (36%), right hemisphere network included 275/1796 (15.3%), occipitotemporal network for complex visual processing 107/1796 (6%), the hippocampal limbic network for amnesias and emotional disorders 397/1796 (22%) and miscellaneous network syndromes 481/1796 (27%). Conclusion – The Coconuts is a valid and practical test of a comprehensive array of known behavioral neurological and neuropsychiatric syndromes in patients with stroke.     

Using videoconferencing to support teachers to conduct preference assessments with students with autism and developmental disabilities

We used widely available videoconferencing equipment to support teachers to conduct preference assessments for three students with autism and developmental disabilities. Supervisors located at a university used videoconferencing equipment to collect data on students’ choice of items, the fidelity of teacher implementation of the assessment protocol, and to provide feedback to the teachers. Preference assessment results suggested a number of potentially reinforcing items for each student. In a second phase of the study, the students were given a routine classroom task to complete (i.e., clean up). The students could choose to complete the clean up task and gain access to a neutral item or one of the highly preferred items identified in the prior preference assessment. All students predominantly chose to complete the task in order to access a preferred item identified in the preference assessment. The results of this classroom intervention validated the results of the preference assessments. The findings of this study provide preliminary support for the use of videoconferencing equipment when supporting teaching personnel during common educational assessments.     

TLR-3 polymorphism is an independent prognostic marker for stage II colorectal cancer

Background

Clinicopathologic stage is still the main parameter to evaluate the prognosis of newly diagnosed colorectal cancer (CRC) patients. Although molecular markers have been suggested for follow up of treated CRC patients, their complete clinical application is still under evaluation.

Materials and methods

To evaluate the association of immune-related genes with CRC prognosis and survival, a total of 19 single nucleotide polymorphisms (SNPs) were genotyped in 614 German patients within the Kiel cohort (POPGEN).

Results

A promoter variant (rs1800872) in the Interleukin-10 (IL-10) gene was associated with an increased lymph node metastasis involvement [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.03-4.2, for carriers of the TT genotype]. More importantly, among 582 followed up patients the SNP rs3775291 in the toll-like receptor 3 (TLR-3) gene was associated with CRC specific survival (150 events). Patients carrying the TT genotype had a 93% increased risk of death compared with the CC carriers [hazard ratio (HR) = 1.93, 95% CI 1.14-3.28]. The observed effect of the TLR-3 variant was restricted to stage II patients (HR = 4.14, 95% CI 1.24-13.84) and to patients who did not receive adjuvant therapy (HR = 3.2, 95% CI 1.4-7.7).

Conclusions

Our results may provide additional candidates for risk assessment in stage II CRC patients for treatment decision. Further validation of the presented findings is warranted.     

Arterial aging: a review of the pathophysiology and potential for pharmacological intervention

This review begins with a perspective on the effects of arterial aging on society and world events over the past century. Until recently, the use of just one technique to measure blood pressure non-invasively limited progress in understanding the mechanisms involved and the potential of antihypertensive drug therapies. New methods for extracting information from the arterial waveform have followed the (re)introduction of arterial tonometry into clinical practice, together with mathematical analysis in the frequency and time domains. These new methods have exposed the phenomenon of aortic stiffening with age, and early wave reflection arising therefrom, and identified it as the major cause of cardiovascular degeneration. Such findings point to arterial aging as a logical target for the treatment and prevention not only of cardiac, aortic and large artery disease, but also of damage to microvessels in the brain and kidney, which in turn leads insidiously to dementia and renal failure, respectively.     

Immune cells participate in the oncosuppressive activity of parvovirus H-1PV and are activated as a result of their abortive infection with this agent

Treatment of cancers by means of viruses, that specifically replicate in (oncotropism) and kill (oncolysis) neoplastic cells, is increasingly gaining acceptance in the clinic. Among these agents, parvoviruses have been shown to possess not only direct oncolytic but also immunomodulating properties, serving as an adjuvant to prime the immune system to react against infected tumors. Here, we aimed to establish whether immunomodulating mechanisms participate in the recently reported therapeutic potential of parvoviruses against pancreatic carcinoma. Using adoptive transfer experiments we discovered that the transfer of splenocytes of donor rats harboring H-1PV-treated orthotopic PDAC tumors could significantly prolong the survival of na?ve tumor-bearing recipients, compared to those receiving cells from mock-treated donors. Closer investigation of immunological parameters in infected donor rats revealed that virus-induced interferon gamma production and cellular immune response played an important role in this effect. These data have also preclinical relevance since abortive H-1PV infection of human peripheral blood mononuclear cells or cocultivation of these cells with H-1PV-preinfected pancreatic cancer cells, resulted in enhancement of innate and adaptive immune reactivity. Taken together our data reveal that oncolytic H-1PV modulates the immune system into an anticancer state, and further support the concept of using parvoviruses in the fight against pancreatic cancer.