Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4+ T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.

Extra-and intracellular Escherichia coli hemolysin expressed by two cloned hly determinants, both under the control of the activator element hlyR, were analyzed. One determinant carried all four hly genes (hlyC, hlyA, hlyB, and hlyD), whereas the other carried only the two genes (hlyC and hlyA) required Wurzburg, 1987).Isolation of extra-and intracellular hemolysin. An overnight culture of E. coli 5K carrying pANN202-812 was inoculated in 20 ml of 2 x YT medium (4) at a dilution of 1:100 and incubated with shaking at 37°C. Samples were taken at various time points in the logarithmic growth phase, and cells were pelleted by centrifugation and discarded. The cell-free supernatants were mixed with 75% ammonium sulfate. Complete precipitation was reached by incubating the mixture on ice for 1 h. The pellets were suspended in 10 ml of TCU buffer (20 mM Tris, 150 mM NaCl, 6 M urea, pH 7.0) and dialyzed overnight against TCU buffer. After 24 h, the hemolytic activity was measured, and the preparations were stored at -70°C. Samples were suspended in TCU buffer, and HlyA was separated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (7 to 15% gradient in the presence of 6 M urea) essentially as described by Laemmli (9). Internal (cell-bound) hemolysin from strains E. coli 5K(pANN202-812), E. coli 5K(pANN202-812/17), and E. coli

Escherichia coli haemolysin (Hlya) is a pore-forming protein which belongs to the family of 'Repeat-toxins' (RTX) (Lo et al., 1987; Lally et al., 1989; Kraig et al., 1990). A model for the pore-forming structure of HlyA has been proposed (Ludwig et al., 1991) which consists of eight transmembrane segments all present in this hydrophobic region of HlyA. We report here that two synthetic peptides of 10 and 8 amino acids in length (Pep1 and Pep2, respectively), which are derived from transmembrane segment V, are able to form pores in an artificial lipid bilayer. In addition, Pep1 exhibits strong haemolytic activity when tested on human red blood cells (HRBCs). The haemolytic activity of Pep1 and of E. coli haemolysin is completely inhibited by antibodies raised against Pep1.