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 thyroglobulin (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→ AKD2F_I (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.