The induction of organ-specific antibodies during the graft-vs.-host reaction.
During the parent (P) into F1 hybrid graft-vs.-host reaction (GVHR), nuclear, leukocyte and erythrocyte autoantibodies are commonly seen. The specificity of these autoantibodies is reminiscent of those found in systemic lupus erythematosus (SLE) patients and SLE-prone mice. Organ-specific antibodies, however, including thyro-globulin (Tg) antibodies do not arise spontaneously. There have been conflicting reports about the ability of exogenous Tg to induce an anti-Tg response during the GVHR. We have re-examined this question in greater detail. Using the murine P----F1 GVHR system, the results of this work demonstrate that mouse thyroglobulin (MTg)-specific antibodies can be induced during a GVHR. However, mice must both be undergoing a GVHR, and have received exogenous MTg. The highest autoantibody response occurs if mice are injected with mouse thyroid extract or purified MTg at the time of P----F1 cell transfer. The anti-MTg response is MTg dose dependent. The ability to induce anti-MTg antibody was not major histocompatibility complex restricted, for both the DBA/2----B6D2F1 (low responder H-2 haplotypes to MTg), and AKR or DBA/2----AKD2F1 (high/low responder----high responder haplotype) GVHR gave similar responses. The anti-MTg titers peaked between days 7-10 and declined thereafter. In contrast, antibodies to dsDNA were not present at this early time, but developed after several weeks. We conclude that organ-specific autoantibodies can be induced during a GVHR if the appropriate antigen(s) are presented near the time of GVHR induction.
Kuppers
R C
RC
Department of Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205.
Suiter
T
T
Gleichmann
E
E
Rose
N R
NR
D000208:Acute Disease; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology; D006087:Graft vs Host Reaction; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D008806:Mice, Inbred AKR; D008811:Mice, Inbred DBA; D009928:Organ Specificity; D013954:Thyroglobulin / Q000276:immunology*
D001323:Autoantibodies; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D013954:Thyroglobulin