Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactive T cell (ATLI) clone obtained from lupus-prone BXSB mice. ATLI cells, either before or after 7-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL 1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) were much more powerful stimulators for ATLI cells on a per cell basis. The T cell stimulating ability ofmacrophages and B cells, but not DCs, was sensitive to T-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱ and CD4 were able to block DC-mediated stimulation of ATL 1 proliferation, indicating cognate recognition between ATL 1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.
This study was undertaken to investigate whether levels of anti-alpha-1,6-glucan antibodies in human sera correlate with rheumatoid arthritis(RA)and systemic lupus erythematosus(SLE).Serum samples were collected from patients with SLE(n=30),RA(n=30)and healthy adult volunteers.IgG,IgA and IgM levels against alpha-1,6-glucan were measured using enzyme linked immunosorbent assays.Anti-alpha-1,6-glucan IgG prevalence was raised in patients with active SLE(73.3%)and RA(60%)compared with healthy controls(13.3%).Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor(r=0.642;p<0.05)in RA patients or anti-nuclear antibodies(r=0.675;p<0.05)in SLE patients was observed.No significant differences in anti-alpha-1,6-glucan-IgA or-IgM levels were noted between different groups.We conclude that anti-alpha-1,6-glucan-IgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity.
Inbred strains of mice and rats are widely used in preclinical investigations evaluating the effectiveness of glycan-based biomecines,however,the glycan specificity repertoires of serum Abs in rodents have not been fully characterized.In the present study,serum antibodies in naïve mice and rats of different inbred strains were analyzed for specificity against 4 representative carbohydrate structures including PGA(1,4-linkeda-D-galactopyranosyluronic acids),b-glucan,mannan anda-glucan(dextran).Mannan was not recognized by serum Abs from any of the mouse and rat strains.Serum IgM in naïve F344,BN and Lewis rats recognized PGA andb-glucan and,less strongly,dextran.High titer circulating IgM against PGA were found in mice of BALB/c,C57BL/6,C3H/NeH and BXSB strains.C3H/NeH was the only strain which also produced low titer IgM against β-glucan and dextran.Age-related production of high titer IgM,IgA and IgG Abs against β-glucan was observed in BXSB mice.Intraperitoneal immunization of BALB/c and C57BL/6 mice with β-glucan elicited strong IgM responses,while immunization with PGA also led to an increase of anti-PGA IgM Ab titers.These results provide useful information on the characteristics of glycan-specific natural antibody repertoires in rodents.