@article{RovitusoDuffySchroeteretal.2015,
  author    = {Rovituso, Damiano M. and Duffy, Catharina E. and Schroeter, Michael and Kaiser, Claudia C. and Kleinschnitz, Christoph and Bayas, Antonios and Elsner, Rebecca and Kuerten, Stefanie},
  title     = {The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {14265},
  doi       = {10.1038/srep14265},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148172},
  year      = {2015},
  abstract  = {B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-\(\beta\) (IFN-\(\beta\))-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders.},
  language  = {en}
}
@article{RottlaenderKuerten2015,
  author    = {Rottlaender, Andrea and Kuerten, Stefanie},
  title     = {Stepchild or prodigy? Neuroprotection in multiple sclerosis (MS) research},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160714850},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148416},
  pages     = {14850-14865},
  year      = {2015},
  abstract  = {Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) and characterized by the infiltration of immune cells, demyelination and axonal loss. Loss of axons and nerve fiber pathology are widely accepted as correlates of neurological disability. Hence, it is surprising that the development of neuroprotective therapies has been neglected for a long time. A reason for this could be the diversity of the underlying mechanisms, complex changes in nerve fiber pathology and the absence of biomarkers and tools to quantify neuroregenerative processes. Present therapeutic strategies are aimed at modulating or suppressing the immune response, but do not primarily attenuate axonal pathology. Yet, target-oriented neuroprotective strategies are essential for the treatment of MS, especially as severe damage of nerve fibers mostly occurs in the course of disease progression and cannot be impeded by immune modulatory drugs. This review shall depict the need for neuroprotective strategies and elucidate difficulties and opportunities.},
  language  = {en}
}
@article{WunschCaspellKuertenetal.2015,
  author    = {Wunsch, Marie and Caspell, Richard and Kuerten, Stefanie and Lehmann, Paul V. and Sundararaman, Srividya},
  title     = {Serial measurements of apoptotic cell numbers provide better acceptance criterion for PBMC quality than a single measurement prior to the T cell assay},
  series = {Cells},
  volume    = {4},
  journal   = {Cells},
  number    = {1},
  doi       = {10.3390/cells4010040},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150213},
  pages     = {40-55},
  year      = {2015},
  abstract  = {As soon as Peripheral Blood Mononuclear Cells (PBMC) are isolated from whole blood, some cells begin dying. The rate of apoptotic cell death is increased when PBMC are shipped, cryopreserved, or stored under suboptimal conditions. Apoptotic cells secrete cytokines that suppress inflammation while promoting phagocytosis. Increased numbers of apoptotic cells in PBMC may modulate T cell functions in antigen-triggered T cell assays. We assessed the effect of apoptotic bystander cells on a T cell ELISPOT assay by selectively inducing B cell apoptosis using α-CD20 mAbs. The presence of large numbers of apoptotic B cells did not affect T cell functionality. In contrast, when PBMC were stored under unfavorable conditions, leading to damage and apoptosis in the T cells as well as bystander cells, T cell functionality was greatly impaired. We observed that measuring the number of apoptotic cells before plating the PBMC into an ELISPOT assay did not reflect the extent of PBMC injury, but measuring apoptotic cell frequencies at the end of the assay did. Our data suggest that measuring the numbers of apoptotic cells prior to and post T cell assays may provide more stringent PBMC quality acceptance criteria than measurements done only prior to the start of the assay.},
  language  = {en}
}
@article{WunschZhangHansonetal.2015,
  author    = {Wunsch, Marie and Zhang, Wenji and Hanson, Jodi and Caspell, Richard and Karulin, Alexey Y. and Recks, Mascha S. and Kuerten, Stefanie and Sundararaman, Srividya and Lehmann, Paul V.},
  title     = {Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity},
  series = {Viruses},
  volume    = {7},
  journal   = {Viruses},
  doi       = {10.3390/v7082828},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151462},
  pages     = {4414 -- 4437},
  year      = {2015},
  abstract  = {Most humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 subsets have been limited by the low frequency of HCMV-specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospot\(^{®}\) assay (ELISPOT) that excels in low frequency measurements, we have established these in a sizable cohort of healthy HCMV controllers. Cytokine recall responses were seen in all seropositive donors. Specifically, interferon (IFN)-\({\gamma}\) and/or interleukin (IL)-17 were seen in isolation or with IL-4 in all test subjects. IL-4 recall did not occur in isolation. While the ratios of T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 cells exhibited substantial variations between different individuals these ratios and the frequencies were relatively stable when tested in samples drawn up to five years apart. IFN-\({\gamma}\) and IL-2 co-expressing polyfunctional cells were seen in most subjects. Around half of the HCMV-specific CD4 cells were in a reversible state of exhaustion. The data provided here established the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 characteristic of the CD4 cells that convey immune protection for successful immune surveillance against which reactivity can be compared when the immune surveillance of HCMV fails.},
  language  = {en}
}