Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. IV. Autoantibodies to nuclear antigens.

We studied the requirements for induction of ANA formation in non-irradiated F1 hybrid mice undergoing a chronic graft-versus-host reaction (GVHR) after the injection of parental-strain lymphocytes. T lymphocytes in the donor cell inoculum were both needed and sufficient for the induction of ANA formation. For optimal ANA formation, the F1 recipient mice had to differ at H-2 from the parental donor strain. ANA belonged to the IgG1, IgG2, IgM and IgA (sub)classes of immunoglobulin. IgG ANA occurred in maximal serum titres of 1 in 5,120. ANA were not donor anti-host alloantibodies. At least some ANA were true autoantibodies, i.e. of F1 origin, because they carried the Ig allotypic markers characteristic of the F1 hybrid recipients. These findings are consistent with the concept that the pathogenic mechanism underlying autoantibody formation during the GVHR is an abnormal T-B-cell co-operation. In this process, donor T cells react against foreign histocompatibility antigens of the F1 recipient and generate non-specific help for B cells, including the autoreactive B cells.