TY - JOUR
T1 - Total lymphoid irradiation and antigen-specific tolerance
T2 - future therapy for experimental myasthenia gravis?
AU - de Silva, Shari
AU - McIntosh, Kevin
AU - Blum, Julia E.
AU - Order, Stanley
AU - Mellits, David
AU - Drachman, Daniel B.
N1 - Funding Information:
The work was supported by grants from the National Institutes of Health: No. 1R01 NS23719, New Investigator Award 2R01 NS20943, Immunology Fellowship Training Award A107247; and a Johns Hopkins Institutional Research Grant: No. RR5378; and from the Greater Washington Chapter of the Myasthenia Gravis Foundation.
PY - 1990
Y1 - 1990
N2 - Total lymphoid irradiation (TLI) is effective in the immunosuppressive treatment of human and experimental autoimmune disorders, including experimental autoimmune myasthenia gravis (EAMG). Under certain circumstances, TLI may facilitate the induction of specific tolerance to antigens present during or shortly after the TLI treatment. This study was designed to determine whether TLI could induce or enhance tolerance to acetylcholine receptor (AChR), the antigen in myasthenia gravis, or to other antigens. We presented the antigens in various potentially tolerogenic forms to rats that were first pre-treated with TLI, or controls treated with sham irradiation. Injection of deaggragated human gamma globulin (HGG), a classical tolerogen, was most effective; it produced antigen-specific tolerance, which was significantly enhanced by pre-treatment with TLI. Injection of HGG coupled to rat peritoneal cells induced a moderate degree of specific tolerance; in this case, pre-treatment with TLI added only nonspecific suppression. In contrast, AChR, either in solubilized form with no adjuvant, or coupled to syngeneic rat pertoneal cells, failed to induce tolerance, and actually primed to immune system system, when given alone or in conjunction with TLI. Subsequent challenge with AChR resulted in an enhanced (secondary) anti-AChR antibody response. These results show that the nature of the antigen itself may predispose to tolerance or to immune stimulation. AChR appears to be highly immunogenic. However, if a tolerogenic fragment or form of AChR can be identified, its use in combination with TLI may result in specific tolerance. If such specific tolerance can be induced during an ongoing autoimmune reaction to AChR, it would be an effective treatment for myasthenia gravis.
AB - Total lymphoid irradiation (TLI) is effective in the immunosuppressive treatment of human and experimental autoimmune disorders, including experimental autoimmune myasthenia gravis (EAMG). Under certain circumstances, TLI may facilitate the induction of specific tolerance to antigens present during or shortly after the TLI treatment. This study was designed to determine whether TLI could induce or enhance tolerance to acetylcholine receptor (AChR), the antigen in myasthenia gravis, or to other antigens. We presented the antigens in various potentially tolerogenic forms to rats that were first pre-treated with TLI, or controls treated with sham irradiation. Injection of deaggragated human gamma globulin (HGG), a classical tolerogen, was most effective; it produced antigen-specific tolerance, which was significantly enhanced by pre-treatment with TLI. Injection of HGG coupled to rat peritoneal cells induced a moderate degree of specific tolerance; in this case, pre-treatment with TLI added only nonspecific suppression. In contrast, AChR, either in solubilized form with no adjuvant, or coupled to syngeneic rat pertoneal cells, failed to induce tolerance, and actually primed to immune system system, when given alone or in conjunction with TLI. Subsequent challenge with AChR resulted in an enhanced (secondary) anti-AChR antibody response. These results show that the nature of the antigen itself may predispose to tolerance or to immune stimulation. AChR appears to be highly immunogenic. However, if a tolerogenic fragment or form of AChR can be identified, its use in combination with TLI may result in specific tolerance. If such specific tolerance can be induced during an ongoing autoimmune reaction to AChR, it would be an effective treatment for myasthenia gravis.
KW - Acetylcholine receptor
KW - Immunosuppression
KW - Myasthenia gravis
KW - Tolerance
KW - Total lymphoid irradiation
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U2 - 10.1016/0165-5728(90)90151-C
DO - 10.1016/0165-5728(90)90151-C
M3 - Article
C2 - 1698818
AN - SCOPUS:0025113879
VL - 29
SP - 93
EP - 103
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
SN - 0165-5728
IS - 1-3
ER -