Effector cells of autoimmune encephalomyelitis in the rat belong to the CD4-positive, OX22-adherent T cell subset.

We characterized the effector cells which mediate experimental autoimmune encephalomyelitis (EAE) on the basis of selective adherence properties. Nylon-nonadherent spleen cells (SpC) from Lewis rats challenged earlier with myelin basic protein (BP) in adjuvant were separated by 'panning' on Petri dishes coated with monoclonal antibody (MAb) OX22. OX22 recognizes high molecular weight forms of the leukocyte-common antigen which is present on several cell types, including the CD4-positive T cells which mediate delayed hypersensitivity reactions. We found that the EAE effector cells were enriched in the OX22-adherent T cell population, which supports the hypothesis that delayed hypersensitivity is important in the pathogenesis of this autoimmune disease.

Autoimmune effector cells. Part 10: Effector cells of autoimmune encephalomyelitis in healthy nonimmune rats.

This paper describes our ongoing investigation of the activation of effector cells of experimental allergic encephalomyelitis (EAE) from nonimmune Lewis rats by sequential culture of spleen cells (SpC) with myelin basic protein (BP) and transfer to syngeneic recipients. We show that SpC initiate the effector cell activation process, whereas thymocytes (Thy) are ineffective. Intermediary recipients of BP-cultured SpC are 'primed' for EAE, but do not develop the disease; this primed state persists for at least 2 months. No evidence was found that suppressor cells account for the failure of the intermediary recipients to develop EAE. The activation process can be inhibited by including monoclonal anti-Ia antibody in the primary culture, indicating that multiple triggering signals are involved in the activation of autoreactive T cells.

Autoimmune effector cells. IX. Inhibition of adoptive transfer of autoimmune encephalomyelitis with a monoclonal antibody specific for interleukin 2 receptors.

This study was conducted to determine whether a monoclonal antibody (MAb) specific for rat interleukin 2 receptors (IL 2R) inhibits the activation of effector T cells that adoptively transfer experimental allergic encephalomyelitis (EAE). MAb OX 39 appears to be specific for IL 2R because it binds to concanavalin A-activated, but not resting, rat lymphocytes and inhibits mitogen- and IL 2-induced proliferation of rat spleen cells. Moreover, this MAb inhibits the in vitro activation of effector cells of EAE by myelin basic protein when added to immune donor spleen cell at the start of 72-hr culture or after 24 hr, but not when added after 48 hr of culture. Other studies employed MAb W3/25, which reacts with the rat helper T cell subset and appears to define the rat homolog of the human CD4 marker present on T4-positive cells. MAb W3/25 also blocks in vitro activation of EAE effector cells, and this blocking effect can be abrogated by adding rat T cell growth factor or partially purified IL 2 to the donor spleen cell cultures. T cell growth factor alone is incapable of activating EAE effector cells. These findings are discussed with respect to the role of lymphokines in the generation of autoreactive T cells.

Autoimmune effector cells. VII. Cells isolated from thymus and spinal cord of rats with experimental allergic encephalomyelitis transfer disease.

Effector cells mediating experimental allergic encephalomyelitis (EAE) were recovered from the thymus glands and spinal cords of Lewis rats immunized with myelin basic protein (BP) and complete Freund's adjuvant (CFA), as demonstrated by adoptive transfer to syngeneic recipients following in vitro activation with BP. The thymic effector cells (TCs) were lymphoblasts. Sequential transfer studies suggested that the effector TCs probably recirculated back to the thymus from the periphery. The transfer of EAE with cells derived from the spinal cords of paralyzed donors indicates that disease-inducing effector cells are present in the target organ.

Regulation of experimental allergic encephalomyelitis. Part 5. Role of the recipient in suppressor cell induction.

Suppressor cells that regulate experimental allergic encephalomyelitis (EAE) are present in spleens of Lewis rats that have recovered from the disease, as demonstrated by adoptive transfer of suppression to normal recipients. However, lethally irradiated recipients (850 rad) of spleen cells from recovered donors are not protected against EAE. Indeed, onset of EAE is accelerated in these irradiated recipients. These findings suggest that the host participates in the suppression of EAE.

Autoimmune effector cells. VI. Transfer of experimental allergic encephalomyelitis with spleen cells activated in mixed lymphocyte cultures.

Although spleen cells (SpC) from Lewis rats that have been immunized with guinea pig myelin basic protein in complete Freund's adjuvant do not transfer experimental autoimmune encephalomyelitis (EAE) to syngeneic recipients, we report that effector cells of EAE can be activated in SpC suspensions during mixed lymphocyte reactions (MLR) to allogeneic SpC. Effector cell activation correlates with interleukin 2 (IL 2) production. The results are consistent with the hypothesis that autoreactive cells may be generated as a result of an immune response to exogenous antigens.