ALLOGENEIC HEMATOLYMPHOID MICROCHIMERISM AND PREVENTION OF AUTOIMMUNE-DISEASE IN THE RAT - A RELATIONSHIP BETWEEN ALLOIMMUNITY AND AUTOIMMUNITY

Conventional allogeneic bone marrow transplantation after myeloablatio n can prevent experimental autoimmunity and has been proposed as treat ment for humans, However, trace populations of donor hematolymphoid ce lls persisting in solid organ allograft recipients have been associate d in some circumstances with therapeutic effects similar to replacemen t of the entire bone marrow. We therefore examined whether inducing he matolymphoid microchimerism without myeloablation could confer the abi lity to resist mercuric chloride (HgCl2)-induced autoimmunity. Brown-N orway (BN) rats were pretreated with a syngeneic or allogeneic bone ma rrow infusion under transient FK506 immunosuppression before receiving HgCl2. They were compared with BN rats receiving either no pretreatme nt (naive) or FK506 alone. Administration of HgCl2 to naive BN rats in duced marked autoantibody production, systemic vasculitis and lymphocy tic infiltration of the kidneys, liver and skin in all of the animals and a 47% mortality. In contrast, BN rats pretreated with HgCl2-resist ant allogeneic Lewis bone marrow and transient FK506 showed less clini cal disease and were completely protected from mortality. More specifi cally, IgG anti-laminin autoantibody production was decreased by 40% ( P < 0.05), and there was less histopathological tissue injury (P < 0.0 05), less in vitro autoreactivity (P < 0.05), less of an increase in c lass II MHC expression on B cells (P < 0.01), and 22% less weight loss (P < 0.01), compared with controls, Protection from the experimental autoimmunity was associated with signs of low grade activation of the BN immune system, which included: increased numbers of circulating B a nd activated T cells before administration of HgCl2, and less autoreac tivity and spontaneous proliferation in vitro after HgCl2.