Biomedical subjects

A Tarkowski

Publications and source records attributed to A Tarkowski.

At least 127 records · Page 7Linked to original sources

PubMed1995

Administration of antibodies to hyaluronanreceptor (CD44) delays the start and ameliorates the severity of collagen II arthritis.

Hyaluronanreceptor (CD44) has been shown to be involved in lymphocyte homing during normal leucocyte circulation and during leucocyte extravasation into sites of tissue inflammation. In addition, interaction with CD44 molecule induces T-cell activation and production of cytokines, such as interferon-gamma. In this study we have examined what influence interaction with the CD44 receptor would have on collagen II-induced arthritis in mice. Mice were immunized with rat collagen II and administered with injections of a monoclonal anti-CD44 antibody. Seventeen days after the outbreak of the disease, all of the anti-CD44 treated animals remained clinically health, whereas 37% of the controls displayed arthritis (P < 0.001). Ten days later the prevalence of arthritis was 26% and 65% (P < 0.05), respectively. Furthermore, the severity of the arthritis was significantly ameliorated by the anti-CD44 treatment. Serum levels of interferon-gamma were significantly higher in collagen II immunized animals having been treated with anti-CD44, compared to the controls. Delayed-type hypersensitivity (DTH) response was significantly decreased in the anti-CD44 treated animals, indicating a functional suppression of T cells. In contrast, T cell independent experimental inflammation was not affected by the administration of CD44 antibodies. Our results suggest that interaction with CD44 down-regulates T lymphocyte/monocyte mediated inflammatory reaction, possibly by triggering of interferon-gamma release.

Animals↗

PubMed1995

Preferential induction of septic arthritis and mortality by superantigen-producing staphylococci.

Staphylococcal enterotoxins A through D (SEA through SED) and toxic shock syndrome toxin-1 display superantigen properties, i.e., they stimulate a great fraction of T cells expressing certain T-cell receptor V beta sequences. Using a newly established rat model of septic Staphylococcus aureus arthritis, we have recently shown that an S. aureus strain producing SEA showed marked arthritogenic properties. In the present study we decided to employ another five S. aureus strains, each one producing a distinct exotoxin. Almost all rats injected with superantigen-producing strains developed arthritis. In contrast, only 20% of rats injected with an S. aureus strain lacking superantigen production displayed mild and transient arthritis. Mortality was preferentially induced among the rats inoculated with the S. aureus strains producing SEB and SED. This study emphasizes that superantigen production is an important virulence factor in the development of septic S. aureus arthritis. Differences concerning mortality between staphylococcal strains producing different exotoxins may be dependent on the degree of activation of the immune system.

Animals↗

PubMed1995

Overexpression of the T-cell receptor V beta 3 in transgenic mice increases mortality during infection by enterotoxin A-producing Staphylococcus aureus.

We have previously demonstrated that staphylococcal enterotoxins contribute to arthritis and mortality during staphylococcal infection. To further explore the mechanism by which bacterial superantigens contribute to the pathogenesis of Staphylococcus aureus septicemia, T-cell receptor V beta 3 transgenic (TGV beta 3) mice and nontransgenic (non-TG) littermates were inoculated intravenously with S. aureus AB-1, which produces large amounts of staphylococcal enterotoxin A, which specifically reacts with T-cell receptor V beta 3. Within 9 days after inoculation, 85% of the TGV beta mice died, compared with 31% of their non-TG littermates (P < 0.01). The high mortality of TGV beta 3 mice was accompanied by elevated bacterial burdens in the blood, spleen, and kidneys. The in vivo kinetics of cytokine mRNA expression was studied by an in situ hybridization technique. Staphylococcal infection gave rise to increased expression of interleukin 1 beta (IL-1 beta) mRNA and sparsely expressed tumor necrosis factor alpha (TNF-alpha), IL-4, and IL-10 mRNAs in both groups. Gamma interferon mRNA expression increased on day 3 and was maintained at a detectable level in the late phase of infection in TGV beta 3 mice, in contrast to non-TG mice. Impressively, significantly higher expression of TNF-beta mRNA in TGV beta 3 mice was noted throughout the course of infection than in non-TG littermates. These findings suggest that overproduction of TNF-beta and gamma interferon, the Th1 cytokines, may play a crucial role in the pathogenesis of septicemia caused by enterotoxin-secreting staphylococci.

Animals↗

PubMed1995

Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rheumatoid arthritis.

OBJECTIVE: To study the effects of sulphasalazine (SASP) on the systemic and mucosal humoral immune systems in patients with rheumatoid arthritis (RA). METHODS: Serum concentrations of interleukin 6 (IL-6), class and subclass specific IgG, IgA and IgM, IgA and IgG antigliadin antibodies and rheumatoid factors (RF) of IgG, IgA (including IgA1 and IgA2 subclasses) and IgM isotypes were measured before and 16 weeks after sulphasalazine (SASP) therapy in 15 female and three male patients with RA. Amounts of immunoglobulins in saliva and jejunal fluid were measured as estimates of mucosal humoral immunity. RESULTS: Serum concentrations of IgA and IgG decreased significantly during SASP therapy and correlated with reduced concentrations of IL-6. In addition, levels of circulating IgA RF, IgA anti-gliadin antibodies and IgM RF decreased significantly after the treatment. In contrast, immunoglobulin levels in saliva and jejunal fluid were unaltered. CONCLUSION: SASP exerts powerful but selective inhibitory effects on systemic immunoglobulin production, whereas no effects on mucosal immunoglobulin production were observed. The decreased systemic B cell activity may be mediated by downregulation of the production of IL-6, a cytokine with Ig switching properties.

Adult↗

PubMed1995

Lateralization of T-lymphocyte responses in patients with stroke. Effect of sympathetic dysfunction?

BACKGROUND AND PURPOSE: A number of clinical observations indicate that stroke affects the course of immune-mediated diseases by lateralization of the disease manifestations, such as arthritis. The purpose of this study was to assess the impact of early stroke on lateralization of immune responsiveness. METHODS: The delayed-type hypersensitivity (DTH) reaction to purified protein derivative was used as an in vivo measure of antigen-specific T-lymphocyte reactivity. Assessment of axon reflex vasodilation was simultaneously used to test for cutaneous sympathetic activity. RESULTS: There were no significant differences with regard to lateralization of DTH reactivity when all stroke patients were tested. However, patients with minor stroke displayed a significant (P < .001) decrease of DTH reaction on the paretic side compared with the contralateral side. In contrast, patients with major stroke showed a significant increase (P = .022) of DTH reaction on the paretic side. Patients with left hemiparesis had a significantly greater (P = .045) DTH response on the affected side than patients with a right hemiparesis. In addition, only the patients with motor deficit but not with sensory deficit or aphasia displayed side differences in DTH responses. When electrically evoked axon reflexes were studied in relation to DTH reactions, a significant correlation (r = .64; P < .001) was found between side asymmetries of DTH responses and side asymmetries of axon reflexes in an innervated skin area. No similar relation was present in skin areas where cutaneous sympathetic activity had been blocked by regional anesthesia. CONCLUSIONS: Early stroke lateralizes T-cell-mediated cutaneous inflammation. This effect depends on (1) the localization of the brain lesion, (2) the clinical course of the disease, and (3) the presence of motor deficit and may be mediated by (4) alteration of the cutaneous sympathetic nerve traffic.

Adolescent↗

PubMed1995

Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke.

BACKGROUND AND PURPOSE: We have previously demonstrated that stroke influences systemic immune responses. The aim of the present study was to investigate patterns of local inflammatory response as a consequence of acute stroke. METHODS: Thirty stroke patients were studied prospectively on days 0 to 3, 7 to 9, 21 to 26, and after day 90 with clinical evaluations, radiological assessments, and analysis of serum and cerebrospinal fluid cytokine levels. RESULTS: Significantly increased levels of interleukin-6 (IL-6) in cerebrospinal fluid (P < .001) were observed in virtually all patients studied compared with healthy control subjects. This increase was observed during the whole observation period but was significantly more pronounced within the first days after stroke onset, with a peak level on days 2 and 3. This initial increase was significantly correlated (r = .65, P = .002) with the volume of infarct measured by MRI 2 to 3 months later. Serum levels of IL-6 in stroke patients were significantly lower than cerebrospinal fluid levels of IL-6 (P = .013) and did not display any significant correlation to the size of the brain lesion. Also, increase in intrathecal but not systemic production of IL-1 beta was observed early during the stroke. Only minor increases of cerebrospinal fluid interferon-gamma levels were observed in two patients. CONCLUSIONS: Our study demonstrates an intrathecal production of IL-6 and IL-1 beta in patients with stroke, supporting the notion of localized inflammatory response to acute brain lesion. In addition, the significant correlation between early intrathecal production of IL-6 and the subsequent size of the brain lesion can be used as a prognostic tool, predicting the size of the brain damage before it is possible to accurately visualize it with radiological methods.

Adult↗

PubMed1995

Stroke induced lateralization of delayed-type hypersensitivity in the early and chronic phase of the disease: a prospective study.

The impact of the acute and chronic phase of stroke on in vivo mediated immune functions was prospectively analysed in patients with mono- and multifocal brain lesions. The cutaneous delayed-type hypersensitivity (DTH) reaction to purified protein derivate was used as an in vivo measure of antigen specific T cell reactivity. Stroke patients have been tested prospectively for DTH reactivity at two separate occasions, 6-12 months apart. Both sides of the body were tested at each occasion. The DTH response on the paretic side changed significantly with time, from being smaller on the paretic side as compared with the contralateral one early after the onset of stroke, to become significantly larger (p = 0.017) in the chronic phase of the disease. In addition, stroke patients showed a significantly larger (p = 0.001) DTH reactivity bilaterally in the chronic phase of the stroke than in the early phase. When patients with single brain lesion and multiple brain lesions were analyzed separately, the increase of DTH reactivity on the paretic side between the 2 challenges was significant (p = 0.016) only in patients with the monofocal disease. We conclude that stroke induces i. an inhibition of DTH reactivity on the paretic side as compared with the non-paretic one in the acute phase but a lateralized enhancement of the DTH reactivity in the chronic phase of the disease, ii. a systemic increase of DTH reactivity in the chronic phase of the disease. Clinical factors positively correlated with these aberrations are: i. right sided, subcortical brain lesion, ii. paresis associated with impaired sensitivity, iii. minor stroke.

Adult↗

PubMed1994

Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop.

Evidence has been obtained that catecholamines and their metabolites are present in single lymphocytes and extracts of T- and B-cell clones by use of capillary electrophoresis with electrochemical detection. Pharmacological inhibition of tyrosine hydroxylase reduces observed catecholamine levels, suggesting catecholamine synthesis by lymphocytes. Intracellular dopamine levels are shown to be increased by extra-cellular dopamine, suggesting a cellular-uptake mechanism. Furthermore, incubation with either dopamine or L-dihydroxyphenylalanine, a precursor of dopamine, results in a dose-dependent inhibition of lymphocyte proliferation and differentiation. Together, these results suggest the presence of an autocrine loop whereby lymphocytes down-regulate their own activity.

B-Lymphocytes↗

PubMed1994

Neutralizing interaction between heparins and myotoxin II, a lysine 49 phospholipase A2 from Bothrops asper snake venom. Identification of a heparin-binding and cytolytic toxin region by the use of synthetic peptides and molecular modeling.

Heparin binds to phospholipase A2 myotoxins from Bothrops asper snake venom, inhibiting their toxic activities. This interaction was investigated using purified myotoxin II, a Lys-49 phospholipase A2 of this venom, and a series of heparin variants, fragments, and other glycosaminoglycans. The binding was correlated to toxin neutralization, using endothelial cells as a target. Myotoxin II binds radiolabeled heparin in solution unselectively, and forms macromolecular complexes with an optimum at a heparin:toxin molar ratio of 1:5. Both O-sulfates and N-sulfates play a role in heparin binding, in the order of importance 2-O-sulfates > 6-Osulfates > N-sulfates. The shortest heparin oligosaccharides interacting with myotoxin II are hexasaccharides. The binding of a neutralizing monoclonal antibody (MAb-3) to myotoxin II was not inhibited by heparin, indicating that the two molecules interact with different sites on the toxin. A synthetic peptide (residues 115-129 in the numbering system of Renetseder et al. (Renetseder, R., Brunie, S., Dijkstra, B. W., Drenth, J., and Sigler, P. B. (1985) J. Biol. Chem. 260, 11627-11634) of myotoxin II displays both heparin-binding and cytolytic activities. It is concluded that heparin neutralizes myotoxin II by binding to a strongly cationic site in the region of residues 115-129, a possible contribution of lysines 36 and 38 suggested by molecular modeling studies. As this cationic region appears to be responsible for the cytolytic activity of the toxin, the present report constitutes the first identification of a cytotoxic region on a phospholipase A2 myotoxin.

Amino Acid Sequence↗

PubMed1994

Neutralization of the cytolytic and myotoxic activities of phospholipases A2 from Bothrops asper snake venom by glycosaminoglycans of the heparin/heparan sulfate family.

Basic phospholipases A2 from the venom of Bothrops asper exhibit skeletal muscle damaging activity in vivo, and cytolytic activity to a variety of cell types in culture. Glycosaminoglycans of the heparin/heparan sulfate family were found to be potent blockers of the cytolytic action in vitro, and, as well, to be able to neutralize the muscle damaging activity of purified myotoxins and crude venom in vivo. However, the neutralizing effect of heparins was more potent in vitro than in vivo. The cytolytic activity of myotoxin II (a lysine-49 phospholipase A2 isoform) and its inhibition by heparin was characterized. The neutralizing effect of heparin did not depend on its anticoagulant activity, since both standard heparin and heparin with low affinity for antithrombin (LA-heparin) had a similar efficiency. Heparan sulfate and low molecular mass heparin (5 kDa) also neutralized myotoxin II. In contrast, different heparin-derived disaccharides were unable to block cytolysis, implying a requirement for a longer carbohydrate chain structure for the interaction with the protein. By affinity chromatography and gel diffusion, it was demonstrated that heparins form a complex with all isoforms of basic venom myotoxins, held at least in part by electrostatic interactions. The phospholipase A2 activity of myotoxin III, a related aspartate-49 isoform from the same venom, was unaffected by heparins, despite the fact that its myotoxic activity was inhibited, indicating a dissociation of the two actions.

Animals↗

PubMed1994

Clonal expansion of T lymphocytes causes arthritis and mortality in mice infected with toxic shock syndrome toxin-1-producing staphylococci.

Erosive arthritis is a common and feared complication of staphylococcal infection. The reason(s) for the progressive course of the arthritis is unknown. It has been recently established that enterotoxins produced by Staphylococcus aureus display superantigen properties leading to stimulation of T cells carrying distinct T cell receptor V beta elements. This finding provides a potential connection between staphylococcal exoproteins and endogenous immune mechanisms participating in the infectious process. We have recently describe successful induction of infections arthritis in mice after intravenous inoculation of a toxic shock syndrome toxin-1 (TSST-1)-producing S. aureus LS-1 strain. Using this model we have now found a clonal expansion of T cells expressing V beta 11+ T cell receptor in the synovial tissue of arthritic mice. The role of TSST-1 as a superantigen inducing oligoclonal expansion was confirmed in an in vitro culture system. The expansion of V beta 11+ T cells proved to be of arthritogenic significance since mice genomically deleted of the V beta 11+ T cells did not develop arthritis and since pretreatment of healthy mice with anti-CD4 or anti-V beta 11 monoclonal antibodies inhibited arthritis. In addition, CD4+ and V beta 11+ T cells showed themselves to be of pathogenic significance in staphylococcal-induced mortality, since mice depleted of such populations showed increased survival. We propose that in hematogenously spread S. aureus-induced arthritis the TSST-1-dependent clonal expansion of CD4+ V beta 11+ T cells is a driving pathogenic force.

Animals↗

PubMed1994

Restricted use of T cell receptor V genes in endomysial infiltrates of patients with inflammatory myopathies.

Inclusion body myositis (IBM), polymyositis (PM) and dermatomyositis (DM) are diseases characterized clinically by progressive muscle weakness and histologically by T lymphocyte infiltrates in striated muscle. The pathogenetic role of these cells is proposed to be cell-mediated cytotoxicity in PM and IBM, but the exact mechanisms of their action are poorly understood. Characterization of the variable regions of T cell receptors (TcR) on the infiltrating lymphocytes may be expected to provide insights into the mechanisms of local activation of the immune system in inflammatory myopathies. Immunohistochemical analysis using a panel of monoclonal antibodies specific for 11 V alpha/beta TcR was performed on cryosectioned muscle biopsy specimens from eight patients with IBM, eight with PM and three with DM. In addition, TcR expression was studied in inflammatory infiltrates in skin biopsies obtained from some of the IBM patients challenged locally with tuberculin. Flow cytometry was used to assess expression of TcR on peripheral blood lymphocytes. All the patients displayed a clear restriction of TcR usage, preferentially limited to V alpha 2 and V beta 3 TcR families in the endomysial, but not in perivascular infiltrates, even within the same muscle specimen. Such a restriction was not found in skin punch biopsies or PBL from the same subjects. Our results suggest that T cells extravasate non-selectively to the skeletal muscle, but once there, only certain TcR families proliferate, presumably after encounter with a locally exposed superantigen.

Gene Expression↗

PubMed1994

Activity of hemorrhagic metalloproteinase BaH-1 and myotoxin II from Bothrops asper snake venom on capillary endothelial cells in vitro.

In vivo, hemorrhagic toxins isolated from snake venoms cause a disorganization of the basal lamina of capillaries, with a concomitant degenerative process of endothelial cells. In this study we investigated the effects of BaH-1, a hemorrhagic metalloproteinase purified from the venom of Bothrops asper, on a murine endothelial cell line of capillary origin. A quantitative cytotoxicity assay based on the release of lactic dehydrogenase was utilized. BaH-1, despite its potent hemorrhagic activity, did not exert direct cytolytic activity on the endothelial cells, even at concentrations as high as 65 micrograms/ml. The only visible effect of BaH-1 on the cultured cells was a relatively slow, moderate detachment of cells, interpreted as a consequence of proteolytic degradation of extracellular matrix components. In contrast, myotoxin II, a lysine-49 phospholipase A2 from the same venom, was clearly cytotoxic to this cell type, albeit being devoid of hemorrhagic activity. These findings suggest that the ability of venom metalloproteinases to induce hemorrhage is not related to a direct cytotoxic action on endothelial cells, and that the rapid degenerative changes of endothelium observed in vivo are probably the result of an indirect mechanism.

Animals↗

PubMed1994

Broad cytolytic specificity of myotoxin II, a lysine-49 phospholipase A2 of Bothrops asper snake venom.

The cytotoxic activity of Bothrops asper myotoxin II, a lysine-49 phospholipase A2 isoform, on different cell types in culture, was investigated. Myotoxin II caused a dose-dependent cytolytic effect on all cell types tested, characterized by rapid release of cytoplasmic lactic dehydrogenase and drastic morphological cell alterations. Quantitative differences in the susceptibility to myotoxin II among cell types fell within a relatively narrow range, and in general, the toxin was cytolytic at concentrations of 50-100 micrograms/ml (3-7 microM), when assays were performed using culture medium as a diluent. Toxin activity was markedly enhanced if phosphate-buffered saline was utilized instead of medium. The cytotoxic activity of myotoxin III, an aspartate-49 isoform from the same venom, on both endothelial cells and skeletal muscle myoblasts was higher than that of myotoxin II, suggesting that, although phospholipase A2 activity is clearly not required for the induction of cell damage, it may have an enhancing role. In contrast to B. asper myotoxins, other basic phospholipases A2 with myotoxic activity in vivo (notexin from Notechis scutatus, and two enzymes isolated from Vipera russelli venom) did not affect endothelial cells and myoblasts. Pretreatment of cells with neuraminidase, tunicamycin, or protamine, did not alter their susceptibility to myotoxin II. At low temperatures (2-4 degrees C) myotoxin II was devoid of cytolytic effect. Washing and neutralization experiments using heparin with low affinity for antithrombin or mouse monoclonal antibody MAb-3 suggest that at low temperatures myotoxin II binds very weakly to the cells, and that its normal interaction with the putative target is probably not only based on charge, but that a membrane penetration event may be required.

Adenocarcinoma↗

PubMed1994

Immunomodulating and anti-inflammatory properties of the sympatholytic compound 6-hydroxydopamine.

The objective of this study was to analyse the anti-inflammatory and immunosuppressive properties of 6-hydroxydopamine (6-OHDA), a well known sympatholytic compound. Collagen type II arthritis, a T cell-dependent autoimmune disease, was significantly suppressed by a short-term administration of 6-OHDA at the time of the disease onset. Similar outcome was observed when in vivo models of T cell-dependent and independent inflammatory reactions were applied. In contrast, long-term pretreatment with 6-OHDA and hence efficient sympatholysis did neither affect the course of arthritis nor the outcome of T cell-dependent and independent inflammatory reactions. These findings, together with evidence of dose-dependent in vitro inhibitory effects of 6-OHDA on lymphocyte proliferation and differentiation, indicate that the anti-inflammatory features of this compound are mediated through a direct action on effector cells rather than by sympatholysis.

Animals↗

PubMed1994

Toxic shock syndrome toxin 1 contributes to the arthritogenicity of Staphylococcus aureus.

Although enterotoxins have been implicated in disease states such as food poisoning and toxic shock syndrome, their role in infectious arthritis is not known. To study the arthritogenic properties of toxic shock syndrome toxin 1 (TSST-1), two pairs of S. aureus strains isogenic for TSST-1 production were injected intravenously into healthy Swiss mice. Mice injected with TSST-1-secreting staphylococcal strains developed more frequent and more severe arthritis than did mice inoculated with the isogenic TSST-1-deficient counterparts. Immunohistochemical analysis of arthritic joints revealed an equal number of infiltrating phagocytes in both groups; however, mice inoculated with TSST-1-producing staphylococci had significantly more (P < .01) interleukin-2 receptor-expressing cells in the inflamed synovium than did mice that received the isogenic counterpart. Thus, TSST-1 is a virulence determinant in S. aureus arthritis in mice. The precise mechanism by which this toxin contributes to the development and progression of arthritis needs further investigation.

Animals↗

PubMed1994

T cell receptor V-gene usage in oral lichen planus; increased frequency of T cell receptors expressing V alpha 2 and V beta 3.

In order to analyse the clonality of T cells in the inflammatory infiltrate of oral lichen planus (OLP), mucosal biopsies were obtained from seven patients with manifest disease. The biopsies were stained with MoAbs directed against 11 different T cell receptor (TCR) V-gene families, anti-CD4, anti-CD8 and IL-2 receptor (IL-2R). For comparison, the frequencies of the different TCR V-families were determined in biopsies from five patients with oral candidosis as well as in peripheral blood from three patients with OLP and from six healthy blood donors (HBD). The occurrence of the investigated TCR V-families varied between 0% and 7% in venous blood obtained from both HBD and OLP patients. T lymphocytes expressing the TCR V beta 3 and V alpha 2 in OLP biopsies were, however, detected in frequencies ranging between 18% and 40% of the total fraction of lymphocytes, a consistent finding for all the OLP infiltrates studied. The other nine TCR V-families examined appeared in low frequencies both in biopsies and in peripheral blood. V alpha 2+ and V beta 3+ cells were often localized adjacent to the basal membrane. In contrast, T cells in Candida-induced lesions did not express a biased TCR distribution, and most V-families studied appeared in frequencies of 0-6%. Thus, T lymphocytes in OLP lesions express a substantially higher frequency of TCR V alpha 2 and V beta 3 than expected from the distribution in blood. The clonal expansion of T cells observed in OLP suggests that a superantigen is involved in the pathogenesis of the disease. Whether this superantigen is of exogenous or endogenous origin needs to be investigated.

Adult↗

PubMed1994

Role of T lymphocytes in experimental Staphylococcus aureus arthritis.

Using a recently developed murine model of haematogenously induced Staphylococcus aureus, the authors have characterized the phenotypes and functional properties of inflammatory cells present in the synovium of arthritic mice. The results show that large numbers of granulocytes and macrophages were observed in the inflamed synovia within 24 h of inoculation of S. aureus strain LS-1. Many of the synovial macrophage-like cells strained for cytoplasmic IL-1 alpha and TNF-alpha. Subsequently (> or = 48 h later), a prominent infiltration of T lymphocytes, predominantly of CD4+ phenotype, was observed. Some of the T lymphocytes stained for IL-2 receptor and intracytoplasmic interferon-gamma (IFN-gamma). Surprisingly, in spite of the severe inflammatory process, very few cells expressed MHC class-II molecules in the arthritic synovia. In addition, in vivo depletion of CD4+ T-cells resulted in a considerably milder course of staphylococcal arthritis. The similarities in the phenotype expression of synovial cells and central role of T-cells in S. aureus arthritis as well as in non-infectious models of arthritis, indicate that the process governing joint destruction is likely to be the same, irrespective of the initial stimulus.

Animals↗