Hemorrhagic autoimmune encephalomyelitis induced by adoptive transfer of activated semiallogeneic spleen cells into irradiated rats.

Using lethal irradiation of recipients, adoptive transfer of experimental allergic encephalomyelitis (EAE) into Lewis (LEW) rats using (LEW x PVG/c)F1 (LPVGF1) spleen cells was successfully achieved. Recipient rats usually developed clinical signs of EAE 5 or 6 days after transfer. The EAE was characterized by the presence of a number of petechiae over the spinal cord. Immunohistochemical examination using OX27, a monoclonal antibody specific for RT1.Ac, revealed the localization of transferred F1 (RT1(1/c] cells in the LEW recipients (RT1(1]. Most of the inflammatory cells in the spinal cord lesions were stained positively for OX27, indicating that they were transferred cells. In mild EAE, more W3/25+ cells were found than OX8+ cells. OX8+ cells were predominant in severe EAE, however. Examination of the spleens of rats that developed EAE by OX27 staining revealed that transferred F1 cells gradually increased in number and reached a maximal level on days 5 and 6. In the spleens of rats that received irradiation and transfer but did not develop EAE, few transferred F1 cells were observed. In addition, bromodeoxyuridine (BrdU)-anti-BrdU immunohistochemistry was employed to demonstrate that cell proliferation really takes place in the spleen. It was revealed that the spleens of the recipients of lethal irradiation and F1 cells contained many BrdU+ cells. Because rats given lethal irradiation alone had extremely few BrdU-positive cells in their spleens, labeled cells in the recipients of radiation and transfer originated from transferred F1 cells. Collectively, these findings strongly suggest that transferred cells previously activated in vitro undergo further proliferation in the lymphoid organs of recipients to bring about the development of EAE.