@article{IpKronerGrohetal.2012,
  author    = {Ip, Chi Wang and Kroner, Antje and Groh, Janos and Huber, Marianne and Klein, Dennis and Spahn, Irene and Diem, Ricarda and Williams, Sarah K. and Nave, Klaus-Armin and Edgar, Julia M. and Martini, Rudolf},
  title     = {Neuroinflammation by Cytotoxic T-Lymphocytes Impairs Retrograde Axonal Transport in an Oligodendrocyte Mutant Mouse},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0042554},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134982},
  pages     = {e42554},
  year      = {2012},
  abstract  = {Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.},
  language  = {en}
}
@phdthesis{Kleen2003,
  author    = {Kleen, Thomas Oliver},
  title     = {Dissociated expression of granzyme B and IFN-gamma by T lymphocytes in HIV-1 infected individuals and its implications for Tc1 effector diversity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8460},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {A CD8+ cell-mediated host defense relies on cognate killing of infected target cells and on local inflammation induced by the secretion of IFN-g. Using assays of single cell resolution, it was studied to what extent these two effector function of CD8+ cells are linked. Granzyme B (GzB) is stored in cytolytic granules of CD8+ cells and its secretion is induced by antigen recognition of these cells. Following entry into the cytosol GzB induces apoptosis in the target cells. It was measured whether GzB release by individual CD8+ cells is accompanied by the secretion of IFN-gƒnƒnand of other cytokines. HIV peptide libraries were tested on bulk peripheral blood mononuclear cells and on purified CD4+ and CD8+ cells obtained from HIV infected individuals. The library included a panel of previously defined HLA class I restricted HIV peptides and an overlapping 20-mer peptide-series that covered the entire gp120 molecule. To characterize the in vivo differentiation state of the T-cells, freshly isolated lymphocytes were tested in assays of 24h duration. The data showed that only ~20\% of the peptides triggered the release of both GzB and IFN-g from CD8+ cells. The majority of the HIV peptides induced either GzB or IFN-g, ~40\% in each category. The GzB positive, IFN-g negative CD8+ cells did not produce IL-4 or IL-5, which suggests that they do not correspond to Tc2 cells but represent a novel Tc1 subclass, which was termed Tc1c. Also the IFN-g positive, GzB negative CD8+ cell subpopulation represents a yet undefined CD8+ effector cell lineage that was termed Tc1b. Tc1b and Tc1c cells are likely to make different, possibly antagonistic contributions to the control of HIV infection. Since IFN-g activates HIV replication in latently infected macrophages, the secretion of this cytokine by Tc1b cells in the absence of killing may have adverse effects on the host defense. In contrast, cytolysis by Tc1c cells in the absence of IFN-g production might represent the protective class of response. Further studies in the field of Tc1 effector cell diversity should lead to valuable insights for management of infections and developing rationales for vaccine design.},
  subject      = {Antigen CD8},
  language  = {en}
}