TY - JOUR
T1 - Tolerance to acetylcholine receptor induced by AChR-coupled syngeneic cells
AU - McIntosh, Kevin R.
AU - Drachman, Daniel B.
N1 - Funding Information:
We gratefully acknowledge the excellent technical assistance provided by Ms. Donna Maurath and Mr. Robert N. Adams and the statistical analysis by Dr. Marla Mclntosh. We thank Ms. Christine Fackler Salemi for assistance in the preparation of the manuscript. This research was supported by National Institutes of Health Grant No. RO1NS23719.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1992/5
Y1 - 1992/5
N2 - Intravenous administration of acetylcholine receptor (AChR)-coupled syngeneic spleen cells induced AChR-specific tolerance in Lewis rats. Injection of 20 × 106 AChR-coupled spleen cells resulted in a significant reduction of the antibody response to AChR when the animals were subsequently immunized with AChR (up to 66% inhibition). Tolerance induced by AChR-coupled cells was antigen-specific: challenge with AChR plus an unrelated antigen, ovalbumin (OVA), resulted in significantly reduced serum antibody titers to AChR but normal or enhanced titers to OVA, compared to controls. Lymphocytes from these rats showed substantially reduced proliferative responses in vitro to AChR, and normal or enhanced responses to OVA. To investigate the role of Ia antigens in tolerance induction, AChR was coupled to Ia-positive or Ia-negative spleen cells. Injection of AChR-coupled Ia-positive cells induced antigen-specific tolerance to AChR; challenge with AChR plus OVA resulted in reduced serum antibody titers and lymphoproliferative responses to AChR, and normal or enhanced titers and cellular responses to OVA. Injection of AChR-coupled Ia-negative cells did not induce tolerance to AChR. These results demonstrate that AChR, which is known to be highly immunogenic, can be rendered tolerogenic without denaturation or linkage to toxic substances. The possible mechanisms of tolerance induced by AChR-coupled spleen cells are discussed.
AB - Intravenous administration of acetylcholine receptor (AChR)-coupled syngeneic spleen cells induced AChR-specific tolerance in Lewis rats. Injection of 20 × 106 AChR-coupled spleen cells resulted in a significant reduction of the antibody response to AChR when the animals were subsequently immunized with AChR (up to 66% inhibition). Tolerance induced by AChR-coupled cells was antigen-specific: challenge with AChR plus an unrelated antigen, ovalbumin (OVA), resulted in significantly reduced serum antibody titers to AChR but normal or enhanced titers to OVA, compared to controls. Lymphocytes from these rats showed substantially reduced proliferative responses in vitro to AChR, and normal or enhanced responses to OVA. To investigate the role of Ia antigens in tolerance induction, AChR was coupled to Ia-positive or Ia-negative spleen cells. Injection of AChR-coupled Ia-positive cells induced antigen-specific tolerance to AChR; challenge with AChR plus OVA resulted in reduced serum antibody titers and lymphoproliferative responses to AChR, and normal or enhanced titers and cellular responses to OVA. Injection of AChR-coupled Ia-negative cells did not induce tolerance to AChR. These results demonstrate that AChR, which is known to be highly immunogenic, can be rendered tolerogenic without denaturation or linkage to toxic substances. The possible mechanisms of tolerance induced by AChR-coupled spleen cells are discussed.
KW - Antigen-coupled syngeneic cell
KW - Immunological tolerance
KW - Myasthenia gravis
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U2 - 10.1016/0165-5728(92)90092-Y
DO - 10.1016/0165-5728(92)90092-Y
M3 - Article
C2 - 1374426
AN - SCOPUS:0026605847
VL - 38
SP - 75
EP - 84
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -