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Background: Destruction of cartilage and bone is a major feature in the advanced stage of rheumatoid arthritis (RA), and joint pain is an important clinical problem of RA patients. However, it is unclear whether pain is mainly due to inflammatory processes or whether bone erosion in the late, destructive[for full text, please go to the a.m. URL], 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Autoimmunkrankheiten und Allergien sind durch eine Storung der immunologischen Toleranz gegen Selbstantigene gekennzeichnet. Durch neue molekularbiologische Untersuchungstechniken ist das Wissen uber die Mechanismen der immunologischen Toleranz in den letzten Jahren enorm gestiegen. Die Herausforderung der Zukunft besteht darin, diese Erkenntnisse in therapeutische Strategien umzusetzen. Der vorliegende Beitrag prasentiert eine Ubersicht zur dominanten Rolle der T-Lymphozyten bei Immuntoleranz und Autoimmunitat, beschreibt die bisherigen experimentellen und ersten klinischen Ergebnisse immunmodulatorischer Therapieansatze und gibt einen Ausblick auf mogliche zukunftige Entwicklungen.

Aim. Labeling of specific monoclonal antibodies or their fragments with suitable radionuclides can be utilized for diagnosis of autoimmune disorders or in preclinical research for elucidation of the role of specific cell types in underlying disease pathophysiology. In contrast to other radionuclides, 89Zr as a marker for positron emission tomography (PET) and protocols for 89Zr production so far have found relatively little interest despite the many advantages of this radionuclide. Methods. We examined the production, separation, and characterization of 89Zr, including supplementation of a commercial Cyclone® 18/9 with a self-made Solid Target System (STS) and the construction of a re-usable target holder. Optimized conditions to reduce undesired long-lived side products were specified. Obtained [89Zr]Zr-oxalate was used for labeling of anti-B cell antibodies with desferrioxamine-p-SCN as a bifunctional chelator. 89Zr-labeled antibodies were injected in DBA/1 mice to examine usability for detection of B cells in vivo by PET. Results. The improved conditions yielded 89Zr of high purity with smaller amounts of long living 88Zr isotope compared to other methods. The antibody labeling procedure yielded crude mixtures containing non-chelated metal, which were separated using desalting columns. Analytical radio-HPLC and TLC revealed 89Zr-labeled antibodies of sufficient purity. PET measurements showed binding of 89Zr-labeled anti-B cell antibodies in tissues with high frequencies of B cells, i.e. in spleen and lymph nodes. Conclusion. Labeling of antibodies directed to specific cell types with 89Zr according to our protocol turned out to be an effective tool for in vivo visualization and tracking of cells in mice by immuno-PET.

The biogenic amine, histamine plays a pathophysiological regulatory role in cellular processes of a variety of immune cells. This work analyses the actions of histamine on γδ-T lymphocytes, isolated from human peripheral blood, which are critically involved in immunological surveillance of tumours.We have analysed effects of histamine on the intracellular calcium, actin reorganization, migratory response and the interaction of human γδ T cells with tumour cells such as the A2058 human melanoma cell line, the human Burkitt's Non-Hodgkin lymphoma cell line Raji, the T-lymphoblastic lymphoma cell line Jurkat and the natural killer cell-sensitive erythroleukaemia cell line, K562.γδ T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood γδ T cells, histamine stimulated Pertussis toxin-sensitive intracellular calcium increase, actin polymerization and chemotaxis. However, histamine inhibited the spontaneous cytolytic activity of γδ T cells towards several tumour cell lines in a cholera toxin-sensitive manner. A histamine H(4) receptor antagonist abolished the histamine induced γδ T cell migratory response. A histamine H(2) receptor agonist inhibited γδ T cell-mediated cytotoxicity.Histamine activated signalling pathways typical of chemotaxis (G(i) protein-dependent actin reorganization, increase of intracellular calcium) and induced migratory responses in γδ T lymphocytes, via the H(4) receptor, whereas it down-regulated γδ T cell mediated cytotoxicity through H(2) receptors and G(s) protein-coupled signalling. Our data suggest that histamine activated γδ T cells could modulate immunological surveillance of tumour tissue.

The exchange of solvent and anions from [89Zr]Zr-oxalate in oxalic acid to [89Zr]ZrCl4 in HCl is a crucial step in the production of 89Zr. A fast and reproducible method using cation instead of anion exchange resin giving a recovery of 98.5 ± 1.1% is described here. Obtained 89Zr was used for labeling a monoclonal antibody directed against CD4+ T helper cells.

T cell recognition of self antigens is a key event in the pathogenesis of autoimmune diseases. To date, the initial events that trigger autoreactive T cells are unknown. The "molecular mimicry" hypothesis predicts that during an infection T cells that recognize both a microbial antigen and a related self peptide become activated and cause autoimmune disease. We have systematically examined the recognition of self antigens by HLA-DR4-restricted T cells specific for peptides of the outer surface protein A (OspA) of Borrelia burgdorferi, the etiological agent of Lyme disease. We used the peptide spot synthesis technique for complete peptide substitution analyses of two immunodominant OspA epitopes. Each amino acid residue of the epitopes was substituted with all 20 naturally occurring amino acids and the altered peptides were tested for recognition by a panel of OspA-specific T cells. The binding motifs (supertopes) revealed by these analyses were used to screen public databases for matching human or murine peptides. Several hundred peptides were identified by this search and synthesized. Of these, 28 were recognized by OspA-specific T cells. Thus, T cell cross-reactivity is a common phenomenon and the existence of cross-reactive epitopes alone does not imply molecular mimicry-mediated pathology and autoimmunity.