Adjuvant Disease--the Paradox of Prevention and Induction with Complete Freund's Adjuvant

Cozine, William Samuel; Stanfield, A. B.; Stephens, C. A. L.; Mazur, M. T.

doi:10.3181/00379727-141-36900

Cited by 10 publications

(6 citation statements)

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“…These fractions were much less protective against the het erologous cells (human mixed strains of C, DT, and PN), although the high doses of lysozyme-solubilized product protected the rats completely against both homologous and heterologous challenge. A similar phenome non has been reported in which pretreatment with tubercle bacilli in sa line [9], wax D in saline [24] and tubercle bacilli even in water-in-oil emulsion [6] can suppress the disease. This phenomenon has been consid ered to be analogous to tolerance or antigenic competition as discussed in detail by Gery and Waksman [9].…”

Section: Discussionsupporting

confidence: 78%

Preparation of Various Fractions from Mycobacterium smegmatis, Their Arthritogenicity and Their Preventive Effect on Adjuvant Disease

Kohashi¹,

Pearson²,

Shimono³

et al. 1976

Int Arch Allergy Immunol

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Cell walls of Mycobacterium smegmatis were able to produce much more severe arthritis in rats than the delipidated cells, whereas cell envelope and cell membrane fractions were unable to produce the disease. The lysozyme-solubilized product was able to produce mild disease with only 30% of incidence with an optimum dose, whereas the higher and the lower doses did not produce the disease. The rats immunized with cell envelope, cell membrane fraction and nonarthritogenic doses of lysozyme-solubilized product were protected against the subsequent homologous and heterologous challenge of delipidated cells. It was discussed that this preventative effect can be the result of antigenic competition between the arthritogenic and nonarthritogenic components of M. smegmatis. On the other hand, all the fractions separated here were able to serve as an immunoadjuvant in terms of inducing delayed hypersensitivity to ovalbumin in guinea pigs.

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Section: Discussionsupporting

confidence: 78%

Preparation of Various Fractions from Mycobacterium smegmatis, Their Arthritogenicity and Their Preventive Effect on Adjuvant Disease

Kohashi¹,

Pearson²,

Shimono³

et al. 1976

Int Arch Allergy Immunol

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“…A substantial body of observations indicates that immunologic phenomena underlie the generation of this experimental disease. These are 1) the invariable latency period of at least 10 days between time of inoculation and onset of disease (12); 2) successful transfer of the disease by lymphoid cells from diseased animals (13); 3) an "immune tolerance-like" phenomenon observed in animals that have been exposed to adjuvant early in life (14,15); 4) the suppression of the disease by heterologous antilymphocytic globulin (16), nonlethal whole body irradiation (17), and immunosuppressive drugs (18,19); 5) the hyperglobulinemia and the massive plasma cell concentration in lymph nodes (20); 6) the inhibition of the development of the disease by the removal of lymph nodes that drain the site of adjuvant inoculation (21); and 7) the fact that disease is produced with greater regularity and severity when smaller amounts of adjuvant are injected directly into 1 or more of the inguinal lymph nodes (22).…”

Section: Discussionmentioning

confidence: 99%

Adjuvant polyarthritis. vii. The role of type ii collagen in pathogenesis

Iizuka

Chang

1982

Arthritis & Rheumatism

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The development of immune response in rats directed toward EL4 cells, after the injection of EL4 cells suspended in a saline/oil emulsion, was enhanced by the incorporation of Mycobacterium into the saline/oil emulsion; the incorporation of type I1 collagen into the salineacetic acid/oil emulsion in concentrations ranging from 0.5-25 pg/ml had no apparent effect on the development of immune response. The incorporation of type I1 collagen into the saline-acetic acidloil emulsion at higher concentrations (100 pg and 1.0 mg/ml) significantly suppressed both the humoral and the cell-mediated immune response. Pretreatment of rats with the maximal subarthritogenic dose of complete Freund's adjuvant prevented the development of arthritis in response to a subsequent injection of an arthritogenic dose of the same adjuvant, but had no effect on the development of type I1 collagen-induced arthritis. These observations suggest that adjuvant arthritis and the type I1 collagen-induced arthritis are distinctly different diseases.Adjuvant arthritis in the rat is believed to arise from an aberrant immune response to antigen(s) whose identity remains elusive. The disease may be the result of a delayed hypersensitivity response to bacilli or The endogenous sensitizing immunogen responsible for the development of adjuvant arthritis has been suggested by Trentham and coworkers ( 3 ) to be type I1 collagen. This conclusion was based on their observations that chronic arthritis in the rat, similar to the classic adjuvant arthritis, can be induced by an oily preparation of type I1 collagen (43) and that rats with classic adjuvant arthritis exhibited cellular and humora1 immunity to homologous type I1 collagen (3). Conversely, Cremer et a1 (6) suggested that collageninduced arthritis is an entity distinct from adjuvant arthritis, dependent upon the unique immunogenicity of type I1 collagen in the rat. Our objective in this investigation was to ascertain whether an autoimmune response to type I1 collagen underlies the pathogenesis of both type I1 collagen-induced and adjuvant-induced polyarthritis in the rat. MATERIALS AND METHODSAnimals. Outbred male Sprague-Dawley rats, 4-8 weeks of age, weighing from 120-250 gm, were purchased from Simonsen Laboratory, Gilroy, CA. These rats were housed in metal cages and given water and standard rat chew ad libitum.

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“…In addition, in SNP-pretreated groups, rats that did develop AA were found to have lower clinical as well as radiographical scores compared with rats ofthe FIA-pretreated control groups (Tables 1 and 2). Interestingly, SOP, an A'-acetylated octapeptide lacking the N-terminal threonine of 11,14,17,19,19,21,23 SNP, did not have any protective capacity (experiment 2, Tables 1 and 2), AA incidence and severity in SOP-pretreated rats were not difTerent from FtA-pretreated controls (Tables t and 2), This points to the specificity of the SNP effect in AA, It has been postulated that suppression of autoimmune disease in animals is usually caused by the induction of tolerance to the autoimmune disease-inducing antigen (Higgins & Weiner, 1988;Thomson et al, 1988;Clayton et al, 1989), i,e, the protection against mycobacteria-induced arthritis after pretreatment with whole mycobacteria or the 65-kD HSP, is due to induction of tolerance (Grey & Waksman, 1967;Cozine et al, 1972;van den Broek et al, 1989), This led us to investigate the cellular immune response of the rats to SNP, SOP and M. tuberculosis in vivo and in vitro after 35 days of pretreatment but before induction of AA and also 35 days after induction of AA, Before induction of AA, SNP-pretreated rats showed a DTH to SNP, but not to M. tuberculosis (Table 3), Normal rats and FIA-pretreated rats did not show a DTH to SNP, An in vitro proliferative response of splenic MNC to both SNP and M. tuberculosis is found in SNP-pretreated rats, but not in normal or FtA-pretreated rats (Table 3), Interestingly, no crossreactivities between SOP and SNP or M. tuberculosis were observed (Table 3), This is consistent with the fact that T cell clones A2b and A2c do not recognize the epitope without the N-terminal threonine (van der , Therefore it can be concluded that the threonine at position of 180 ofthe 65-kD mycobacterial HSP is important for immunogenicity of the nonapeptide.…”

Section: Resultsmentioning

confidence: 99%

Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat-shock protein

Yang

Gasser

Feige

1990

Clinical and Experimental Immunology

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SUMMARYAdjuvant arthritis in Lewis rats is a model of T cell-mediated autoimmune arthritis resembling human rheumatoid arthritis, A nonapeptide from the 65-kD heat-shock protein of Mycobacterium bovis BCG, amino acid sequence 180-188, has been described to carry the dominant immunogenic epitope(s) for both arthritis-protective and arthritogenie T cell clones. Here we demonstrate that immunizations with the synthetic nonapeptide completely protected rats against adjuvant arthritis induced by M. tuberculosis. Interestingly, deletion of the N-teminal threonine of the nonapeptide resulted in loss ofthe protective activity, Pretreatments with the nonapeptide resulted in an immune response to the nonapeptide and to M. tuberculosis. After immunizations with the synthetic nonapeptide, only low titres of nonapeptide-specific antibodies were produced, whereas a significant cellular immune response to the nonapeptide was observed. In addition, the protection was transferable to naive rats by spleen T cells. These findings document the requirement of a T cellspecific immune response to the dominant epitope ofthe 65-kD mycobacterial heat-shock protein for the protection against adjuvant arthritis and suggest the feasibility of immune intervention in autoimmune arthritis through the use of synthetic peptides.

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Adjuvant Disease--the Paradox of Prevention and Induction with Complete Freund's Adjuvant

Cited by 10 publications

References 0 publications

Preparation of Various Fractions from <i>Mycobacterium smegmati</i><i>s</i>, Their Arthritogenicity and Their Preventive Effect on Adjuvant Disease

Preparation of Various Fractions from <i>Mycobacterium smegmati</i><i>s</i>, Their Arthritogenicity and Their Preventive Effect on Adjuvant Disease

Adjuvant polyarthritis. vii. The role of type ii collagen in pathogenesis

Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat-shock protein

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