ADOPTIVE TRANSFER OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - RECIPIENT RESPONSE TO MYELIN BASIC PROTEIN-REACTIVE LYMPHOCYTES

We have used adoptive transfer of myelin basic protein (MBP)-reactive lymphocytes in the Lewis rat model of experimental allergic encephalom yelitis (EAE) to identify stages of effector cell development and to i nvestigate the nature of the subsequent recipient response to the tran sferred cells. Depending on the timing of cell collection, lymph node cells (LNC) obtained from MBP-CFA (MBP emulsified in complete Freund's adjuvant)-immunized donors may directly transfer clinical disease; ho wever, independent of disease development, recipients of LNC develop e arly onset of clinical disease following immunization of the recipient s with MBP-CFA, consistent with the presence of MBP-memory cells in th e LNC transfer inoculum. Similarly obtained spleen cells do not direct ly transfer disease and do not contain MBP-memory cells (as defined by the early onset of clinical disease following MBP-CFA challenge). Spl een cells adoptively transfer clinical disease only following in vitro culture stimulation with antigen or selected mitogens. Recipients of the primary culture-derived encephalitogenic spleen cells also develop an accelerated onset of clinical disease following MBP-CFA challenge, indicative of the presence of MBP-memory cells, and are not vaccinate d. Encephalitogenic T cell lines adoptively transfer clinical disease, and in most cases recipients are vaccinated to MBP-CFA-induced active disease, but remain susceptible to adoptively transferred disease. Co -transfer of encephalitogenic T cell line cells with MBP-reactive lymp h node or encephalitogenic spleen cells does not alter the vaccination response. We have found that during the process of T cell line develo pment, the vaccinating phenotype is acquired following the second anti gen stimulation cycle. These studies also demonstrate that regulation induced by T cell vaccination blocks the development of effector cells from precursor cells and that such regulation is also equally effecti ve in blocking disease development in recipients which have increased numbers of memory cells. Thus, the response to T cell vaccination, onc e established, is fully capable of inhibiting the development of effec tor cells from increased numbers of precursor/memory cells, a response that would be needed in the clinical application of vaccination-induc ed resistance.