Temporal dissociation of experimental allergic encephalomyelitis transfer activity and gamma globulin staining of lymphoid cells from sensitized Lewis rats

The occurrence of peak EAE transfer activity in LNC several days after time of maximum staining for γ globulin suggests that the factor(s) responsible for transfer of EAE lesions is distinct from conventional immunoglobulins. This finding provides a clear explanation for our earlier observation, viz., anti-rat γ globulin serum does not alter EAE transfer activity of D9 LNC (1). We are aware that we have no evidence as to whether any of the γ globulin demonstrated in LNC represents antibody specifically reactive with nervous tissue. Our findings agree with that of Oldstone and Dixon (unpublished) that antibody reactive with brain is demonstrable in thoracic duct lymph of Lewis rats only between 5 and 7 days after sensitization. At no time could they find such antibody in blood serum. Based on the results here reported (Table I), it is conceivable that two different immune responses, i.e., antibody production and delayed-type hypersensitivity, account for development of clinical neurologic signs and lesions, respectively—both being essential for occurrence of typical EAE. Under the conditions we employed for LNC transfer of EAE during the past 8 years, occurrence of paralytic signs has been a rare event in recipient Lewis rats receiving D9 LNC. This is true despite the fact that many animals develop severe lesions of EAE throughout the brain and spinal cord. Recent work has shown that phytohemagglutinin injected simultaneously with spinal cord-adjuvant markedly suppresses clinical signs of EAE in Lewis rats but has little, if any, effect on development of lesions of the disease (G. O. Westenfelter, P. Y. Paterson and D. G. Drobish, to be published). Bornstein and Crain (4) have reported a dissociation between serum factors causing synaptic blockade and those causing demyelination when acute phase EAE serum is added to myelinating and electrically active nervous tissue cultures. Pabst and Dupuy (5) have described production of paralytic, often lethal, disease without appreciable histologic changes in guinea pigs injected with plasma derived from donors sensitized to nervous tissue and given lethal doses of x-irradiation. Finally, Brown et al. (6) and Tung and Unanue (7) have secured strong evidence that in another well established experimental autoimmune disease, allergic orchitis, both antibody and sensitized lymphoid cells must act in concert in order for the full-blown disease to occur.