摘要:

Background: Insulin-dependant diabetes mellitus (IDDM) is an autoimmune disease that can be altered by immune modulation. NOD mice and BB rats have been used as models of spontaneous IDDM. The development of diabetes in these animals has been altered by several different immune modulators using relatively high doses for the size of the animal. The effect of pharmaceutical doses of vaccines on the development of diabetes in these rodents has not been adequately studied.Methods: I studied the effect of administering killed human vaccines using low concentrations and as few as 3 doses.Results: Administration of human vaccines to diabetic prone newborn animals starting before 2 weeks of age prevented the development of diabetes while administration of the pertussis vaccine starting at 8 weeks of life was associated with an increased incidence of diabetes.Conclusions: Animal studies have demonstrated the timing and content of human vaccines can affect the development of diabetes. Clinical trials of new human vaccines are not designed and generally not powered to detect an effect of immunization on the development of IDDM. These animal toxicology studies indicate that the effect of vaccines on human insulin dependent diabetes needs to be examined.

ISSN:0891-6934    

DOI:10.3109/08916939608995359

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both idiopathic and associated with other diseases (B and T lymphoma, B hepatitis, gastric carcinoma, systemic lupus erythematosus) or a-methyldopa therapy, in order to value T- and B-cell activation. We determined the count of T- and B-cell subsets in peripheral blood, the proliferative response of peripheral blood lymphocytes (PBL) to phytohe-magglutinin (PHA) and to pokeweed mitogen (PWM), the percentage of CD25+cells in culture and interleukin (1L)-lα, IL-2, IL-4, tumor necrosis factor (TNF)αand soluble IL-2 receptor (sIL-2R) levels in sera and in culture. Except for an increase in CD4+and CD8+T cell number in a case of AIHA associated with a T lymphoma and an increase in the percentage of CD5+and PCAl+B cells in two cases of AIHA associated with B lymphoma and with SLE, no further data showed a relationship with the disease possibly associated with AIHA, so both idiopathic and secondary AIHA cases were analyzed together. CD4+T cells were reduced in number in 9 cases, while CD8+T cells were reduced in 6 cases. The percentage of CD5+B cells was increased in 5 cases. The percentage of PCAl+cells was increased in all cases (mean±sd: 18±22 vs 0,2±1 in controls). The average PBL proliferative response to PHA was reduced (S.I. 71±55 vs 138±45 in controls) as well as that to PWM (S.I. 27±21 vs 75±24 in controls), despite IL-2 high levels, in all cases, in both sera (meanfsd: 648±351 pg/ml vs 16±4 pg/ml in controls) and culture supernatants (meanksd: 1045 f 677 pg/ml vs 195±51 pg/ml in controls). In PHA stimulated cultures the percentage of CD25+cells was reduced (meanasd: 37±18 vs 63±14 in controls), sIL-2R levels were like controls in 7 cases. In sera sIL-2R levels were increased in all cases (meanfsd 1256±465 U/ml vs 256±114 U/ml in controls), IL-lαwas increased in all cases too, while IL-4 levels were increased only in 7 cases. Linear regression analysis generally showed a low relationship between S.I. and IL-2, IL-4 and sIL-2R levels in supernatants of PHA stimulated culture as well as between S.I. and the percentage of CD25+cells. Taken together these data suggest a state of B- and T-cell hyperactivation in AIHA. The low PBL proliferative responsein vim, explained in previous studies as a temporary functional exhaustion, might be itself a sign of the complete lymphocyte activation occurringin vivoin AIHA.

ISSN:0891-6934    

DOI:10.3109/08916939608995360

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We investigated the effect of oral administration of type I interferon (IFN) in experimental allergic neuritis (EAN) in Lewis rats immunized with bovine peripheral nerve myelin. Starting at 7 days preceding immunization, rats were fed daily until sacrifice either with 5000 U rat IFN-α/βor mock-IFN. The clinical severity of EAN was significantly reduced in IFN-α/βfed animals compared to mock-IFN fed controls. Demyelination, but not inflammation, was decreased in IFN-α/βfed compared to mock-IFN fed rats at day 20 after immunization.In situIFN-γproduction and inflammation were reduced when evaluated by immunocytochemistry at day 13 after immunization. Spleen cells from IFN-α/βfed compared to mock-IFN fed EAN rats showed significantly reduced proliferation to stimulation with Con A or peripheral nerve myelin. IFN-γproduction in draining lymph node cells was significantly reduced after stimulation with bovine peripheral nerve myelin. Our data suggest that oral administration of IFN-α/βreduces the severity of EAN, possibly by a reduction in production.

ISSN:0891-6934    

DOI:10.3109/08916939608995361

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We report herein the characterization of a human IgG antibody reactive with a nonmuscle 135 kD microfilament-associated protein, anti-135 kD. Using nonmuscle epithelial PtK2 cells as substrate in indirect immunofluorescence, we identified a distinctive pattern of reactivity with microfilaments in sera from 12 of 165 (7.3%) patients investigated for systemic autoimmune diseases and in only 2 of 171 (1.2%) normal and rheumatic disease controls (P<0.006, 95% CI 1.46 to 30.1). An association between anti-135 kD and Raynaud's phenomenon (n= 12/14, 85.7%) with or without an associated systemic autoimmune disease was noted. The anti-135 kD specificity was established by several criteria. (1) The fluorescence was periodically distributed along microfilaments and concentrated at focal adhesions for all sera (n = 14). (2) On immunoblots, the 14 sera reacted with a PtK2 polypeptide of 135 kD. (3) IgC purified by blot-affinity from the 135 kD band (a-135) reproduced the fluorescent pattern of the original sera while IgG purified from other bands did not. (4) Double immunofluorescence with a-135 and anti-α-actinin mAb indicated absence of antibody fluorescence at ruffling membranes whereα-actinin was distributed. (5) IgG subclass analysis of anti-135 kD revealed that 12 (85.7%) sera are of IgC3 isotype and 2 (14.3%) are of IgGl isotype while the light chain expression was K restricted. This is the first report of an antibody to a 135 kD microfilament protein. Anti-135 kD expand the repertoire of anti-microfilament and anticytoskeletal antibodies in human sera.

ISSN:0891-6934    

DOI:10.3109/08916939608995362

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Integrin-adressin binding is a critical step in lymphocty attachment to target tissues. The mucosal recognition systems (αEβ7,α4β7, MADcam-1) have been implicated in the autoimmue process in rheumatoid arthritis. We developed a model forin vivostudy of radio-labelled lymphocyte circulation and their attachment to human rheumatoid synovium. We studied the homing of tonsil lymphocytes, considered as mucosal lymphocytes, and the involvement ofαEβ7 integrin and LFA1 in the homing of tonsil lymphocytes.We engrafted human rheumatoid synovium subcutaneously in 6 week old SCID CB17 mice. Three weeks later, we injected intraperitoneally 20 IO6human peripheral blood or tonsil mononuclear cells, previously labelled with 3 mCFi HMPAO-99mTc. A mouse total body scintigram was obtained 20 h postinjection. The same protocol was performed after treatment of the MNC and mAb against LFA-1 (CD11a) orαEβ7 (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post-injection was enhanced compared to blood MNC (12731±8297 cpm/200 pixel) versus 5982±4713 cpm/200 pixel, p<0.05). A monoclonal antibody against LFA 1 decreased the activity in the graft (4152±1287 cpm/200 pixel), p<0.05. No significant difference in tonsil MNC attachment to rheumatoid synovial tissue was observed with a mAb againstαEβ7 (8057±5009 cpm/200 pixel).Our results showed an increase in radiolabelled mucosal MNC migration in synovial tissue engrafted in SCID mice compared with blood MNC. Moreover, the date suggest that LFA-1 but not theαEβ7 integrin is involved in tonsil MNC binding to synovial tissue in RA.

ISSN:0891-6934    

DOI:10.3109/08916939608995363

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Insulin-dependent diabetes mellitus (IDDM) is a major cause of morbidity and mortality from long-standing complications. The autoimmune nature of IDDM has encouraged use of immunosuppressive and antiinflammatory strategies to better preserve residual pancreatic p-cell function at the time of diagnosis. Fusidic acid and its sodium salt, fusidin, is a relatively atoxic antibiotic used mainly in the treatment of staphylococcal infections. Recently, fusidin has been demonstrated to possess immunosuppressive functionsin vitroandin vivo, and the drug has shown promise in preventing the disease in animal models of IDDM and in a preliminary trial in IDDM patients.

ISSN:0891-6934    

DOI:10.3109/08916939608995364

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939608995365

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor