Cross-sectional and longitudinal analysis of myelin-reactive T cells in patients with multiple sclerosis.

Activated myelin-specific T cells are thought to mediate inflammatory tissue damage in multiple sclerosis (MS). Applying a large panel of myelin antigens, we demonstrate the direct ex vivo detection of viable IFN-gamma/TNF-alpha producing CD4+/CD69+ T cells 6 hours after antigenic challenge, by intracellular flow cytometry in 3/33 MS patients and 2/26 healthy controls with calculated frequencies of (mean +/- SEM): 0.031% +/- 0.

Death ligand TRAIL induces no apoptosis but inhibits activation of human (auto)antigen-specific T cells.

TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, induces apoptosis in susceptible cells, which can be both malignant and nontransformed. Despite homologies among the death ligands, there are great differences between the TRAIL system on the one hand and the TNF and CD95 systems on the other hand. In particular, TRAIL-induced apoptosis differs between rodents and man.

Differential regulation of myelin phagocytosis by macrophages/microglia, involvement of target myelin, Fc receptors and activation by intravenous immunoglobulins.

Macrophages/microglia are the key effector cells in myelin removal. Differences exist in the amount and time course of myelin uptake in the central (CNS) and peripheral nervous system (PNS), the basis of this difference, however, is not yet clarified. In the present experiments we studied the phagocytosis rate of CNS or PNS myelin by macrophages and microglia in vitro.

Induction of TRAIL-mediated glioma cell death by human T cells.

Among the death ligands of the tumor necrosis factor/nerve growth factor (TNF/NGF) superfamily, TNF-related apoptosis-inducing ligand (TRAIL) is considered to play a unique role due to its binding to both apoptosis-inducing and -blocking membranous receptors, apoptosis-independent effects and distinct species differences. Here, we demonstrate that human antigen-specific T helper cells upon activation are capable of directly lysing glioma cell lines via TRAIL receptor/TRAIL interactions. Out of 17 T cell lines, nine showed predominantly TRAIL-mediated killing of glioma cell lines compared to CD95 ligand- or TNF-induced cell death.

Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins.

Bacterial heat shock proteins (hsp) are evolutionary conserved immunodominant proteins that manifest amino acid homologies with hsp present in mammalian cells. Preimmunization with mycobacterial hsp65 has been found to protect against various forms of experimental arthritis. As these protective effects have previously been attributed to induction of self homologue cross-reactive T cell responses, the question was raised as to whether this protective effect could be extended to other highly conserved and immunodominant microbial Ags with mammalian homologues.