B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: implications for the lesion pathogenesis of multiple sclerosis

The co-inhibitory B7-homologue 1 (B7-H1/PD-L1) influences adaptive immune responses and has been proposed to contribute to the mechanisms maintaining peripheral tolerance and limiting inflammatory damage in parenchymal organs. To understand the B7-H1/PD1 pathway in CNS inflammation, we analyzed adaptive immune responses in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced EAE and assessed the expression of B7-H1 in human CNS tissue. B7-H1(-/-) mice exhibited an accelerated disease onset and significantly exacerbated EAE severity, although absence of B7-H1 had no influence on MOG antibody production. Peripheral MOG-specific IFN-gamma/IL-17 T cell responses occurred earlier and enhanced in B7-H1(-/-) mice, but ceased more rapidly. In the CNS, however, significantly higher numbers of activated neuroantigen-specific T cells persisted during all stages of EAE. Experiments showing a direct inhibitory role of APC-derived B7-H1 on the activation of MOG-specific effector cells support the assumption that parenchymal B7-H1 is pivotal for delineating T cell fate in the target organ. Compatible with this concept, our data investigating human brain tissue specimens show a strong up-regulation of B7-H1 in lesions of multiple sclerosis. Our findings demonstrate the critical importance of B7-H1 as an immune-inhibitory molecule capable of down-regulating T cell responses thus contributing to the confinement of immunopathological damage.     

Effects of green tea polyphenols on murine transplant-reactive T cell immunity

Green tea polyphenols (GrTP), the active ingredient of green tea, may have immunosuppressive properties, but whether and how GrTP affect transplant-reactive T cells is unknown. To address this, we tested the effects of GrTP on in vitro and in vivo transplant-reactive T cell immunity. GrTP inhibited IFNgamma secretion by cultured monoclonal T cells and by alloreactive T cells in mixed lymphocyte reactions. Oral GrTP significantly prolonged minor antigen-disparate skin graft survival and decreased the frequency of donor-reactive interferon gamma-producing T cells in recipient secondary lymphoid organs compared to controls. In contrast to other hypothesized actions, oral GrTP did not alter dendritic cell trafficking to lymph nodes or affect metalloproteinase activity in the graft. This is the first report of an immunosuppressive effect of GrTP on transplant-reactive T cell immunity. The results suggest that oral intake of green tea could act as an adjunctive therapy for prevention of transplant rejection in humans.     

Antibody-binding epitope differences in the nucleoprotein of avian and mammalian influenza A viruses

Abstract Influenza virus nucleoprotein (NP) binds to the viral genome RNA and forms the internal ribonucleoprotein complex of the virus particle. Avian and human influenza virus NP have characteristic differences at several amino acid positions. It is not known whether any of these differences can be recognized by antibodies. In the present study five monoclonal antibodies (MAbs) were produced against NP of A/Duck/Novosibirsk/56/05 (H5N1) influenza virus. Two MAbs discerned human and avian influenza strains on ELISA testing. The NP expressed in a prokaryotic system was used for the analysis of site-specific mutants carrying amino acid substitutions in the relevant positions. Amino acid residues in positions 100 and 101 were shown to be recognized by the MAbs. The residue in position 100 is host-specific, and its recognition by the MAb 2E6 may be useful for the differentiation of human and avian viruses. The data are discussed in view of the effects of amino acid substitutions in influenza virus NP affecting both host range and antibody-binding specificity.     

Localization of HTLV-1 and HIV-1 Proviral Sequences in Chromosomes of Persistently Infected Cells

Integration sites for HTLV-1 and HIV-1proviruses were detected by FISH on the chromosomes of HTHIV27 cells persistently infected by HIV-1 (strain IIIB). HTLV-1 signals were found on 9 loci of chromosomes 4, 6, 9, 15 and 16. Integration sites of GC-rich HTLV-1 provirus are located in GC-rich isochores, confirming an ‘isopycnic’ integration, namely an integration in which the GC level of the host sequences around the integration site match the GC level of the provirus. This conclusion is not only derived from the compositional map of human chromosomes, but also from HTLV-1 hybridization on compositional fractions of human DNA. Integration of GC-poor HIV- 1 provirus was found on 4 loci of chromosomes 2, 7, 17 and 19. One copy of a complete HIV-1 provirus, which is active, was integrated in H1 isochores, whereas other defective copies were located in GC-poor L isochores. These results are discussed in terms of regional integration of retroviral sequences. This revised version was published online in August 2006 with corrections to the Cover Date.     

Does exercise evoke neurological symptoms in healthy subjects?

Concussion is a common injury in collision sports and is evidenced by a variety of signs and symptoms. The recording of neurological symptoms is an important component of screening for a concussion and in return-to-play decisions. However similar symptoms are prevalent in the general population and are reported to be associated with participation in physical activities. The purpose of this study was to document the neurological symptoms reported by healthy individuals following controlled bouts of exercise. A crossover randomised design with 2 levels of exercise intensity, moderate intensity and high intensity, each of 15 min duration was used. Participants completed a standardised postconcussion symptom checklist prior to exercise (pre), immediately following exercise (post-1) and again after 15 min of rest (post-2). 60 participants were recruited into the study. A summed symptom score was calculated and analysed with a 2-way repeated measures ANOVA procedure. The intensity × time interaction (F_2,118 = 23.94, p < 0.001) demonstrated a significant increase in symptom scores for the high intensity condition immediately following exercise (p < 0.001). Although the moderate intensity showed a similar trend this was not significant. These findings suggest that sports medicine professionals need to be aware of the effect of exercise on symptom reporting when assessing and in making return-to-play decisions.     

The role of regulatory T cells in multiple sclerosis

The dysregulation of inflammatory responses and of immune self-tolerance is considered to be a key element in the autoreactive immune response in multiple sclerosis (MS). Regulatory T (T(REG)) cells have emerged as crucial players in the pathogenetic scenario of CNS autoimmune inflammation. Targeted deletion of T(REG) cells causes spontaneous autoimmune disease in mice, whereas augmentation of T(REG)-cell function can prevent the development of or alleviate variants of experimental autoimmune encephalomyelitis, the animal model of MS. Recent findings indicate that MS itself is also accompanied by dysfunction or impaired maturation of T(REG) cells. The development and function of T(REG) cells is closely linked to dendritic cells (DCs), which have a central role in the activation and reactivation of encephalitogenic cells in the CNS. DCs and T(REG) cells have an intimate bidirectional relationship, and, in combination with other factors and cell types, certain types of DCs are capable of inducing T(REG) cells. Consequently, T(REG) cells and DCs have been recognized as potential therapeutic targets in MS. This Review compiles the current knowledge on the role and function of various subsets of T(REG) cells in MS and experimental autoimmune encephalomyelitis. We also highlight the role of tolerogenic DCs and their bidirectional interaction with T(REG) cells during CNS autoimmunity.     

Community exercise programing and its potential influence on quality of life and functional reach for individuals with spinal cord injury*

Context/Objective: After an individual with a Spinal Cord Injury (SCI) participates in the initial rehabilitation process, they often experience limited access to physical therapy services and other fitness activities. The purpose of this study was to examine previously collected data for changes in quality of life (QoL) and functional reach in individuals with SCI following an 8-week community exercise program.

Design: Secondary analysis of previously collected data.

Setting: Community-based exercise program.

Participants: Twenty-two participants with an average of 9 years post-SCI, both complete and incomplete injuries, and injury levels ranging from C2 to L5.

Interventions: Participants completed an 8-week program, once per week for 4 hours that included a four-station circuit of resistance training, aerobic exercise, trunk stability, and education.

Outcome Measures: Physical function was measured using the modified Functional Reach Test (mFRT). QoL was measured with the Life Satisfaction Questionnaire-9 (LiSAT-9).

Results: The mFRT improved by 2 inches (±7.04) P?<?0.001 and QoL improved as well, P?<?0.001.

Conclusion: The findings of this study are consistent with the hypothesis that a supervised post-rehabilitation community exercise program, like Spinal Mobility, may positively impact the QoL and functional reach in individuals with SCI.     

Traumatic intracranial hemorrhage in patients with seizures: descriptive characteristics

We reviewed the records of all patients with recurrent seizures and severe head injury-induced traumatic intracranial hemorrhage (TIH) between 1989 and 2003 in three Israeli medical centers. We identified 52 cases (44 males, mean age=43+/-19 years, range=8-84; 8 females; mean age=74+/-12 years, range=48-85). Twenty-seven (52%) had additional known risk factors for TIH, e.g., older age, alcohol abuse, and anticoagulant use. All five children and adolescents had mental retardation. Approximately one-half of patients with seizures and TIH have additional risk factors for TIH. Non-mentally retarded children and adolescents with seizures are probably at low risk of developing TIH. Women less than 70 years old with seizures are much less prone to TIH than men. In young "otherwise healthy" patients with epilepsy, suboptimal treatment seems to be an important factor in the occurrence of TIH.