Activation of effector cells in experimental allergic encephalomyelitis by interleukin 2 (IL-2).

The ability of both spleen and lymph node cells of Lewis rats immunized with basic protein (BP) to transfer experimental allergic encephalomyelitis (EAE) after in vitro culture with Con A was shown to be dependent on the generation of IL 2. The inability of lymph node cells, in contrast to spleen cells of sensitized donors, to transfer EAE after in vitro culture with 2 µg/ml Con A is the result of the generation of effective levels of IL 2 by the latter but not the former cell population under these conditions. However, when BP-sensitized lymph node cells were cultured with 2 µg/ml Con A in the presence of normal spleen cells, they could transfer EAE to naive recipients. Furthermore, supernatants of Con A-activated normal spleen cells, when cultured with BP-sensitized lymph node cells, condition the latter cells as well as spleen cells to transfer EAE. This transfer of EAE was also effected by culturing the BP-sensitized lymph node and spleen cells with IL 2 isolated from supernatants of Con A-activated normal spleen cells. Neither normal spleen nor lymph node cells cultured with IL 2 were capable of transferring EAE. Under certain conditions lymph node cells can be activated directly to produce IL 2. However, the conditions required for proliferation of lymph node cells and their generation of IL 2 differ from those required for activation of spleen cells in both the dose requirement of Con A and kinetic patterns. Whereas maximal activation of spleen cells occurred at 3 days with 2 µg/ml Con A, the maximal activation of lymph node cells occurred at 2 days and required 10 µg/ml Con A. The addition of 10 µg/ml of Con A to BP-sensitized lymph node cells resulted in a higher production of IL 2 than that produced by spleen cells under optimal conditions. Culturing of BP-sensitized lymph node cells with 10 µg/ml Con A permitted the transfer of EAE by these cells and resulted in the generation of IL 2, which was effective in conditioning both BP-sensitized lymph node and spleen cells to transfer the disease. The ability of IL 2 to condition BP-sensitized lymphocytes to transfer EAE is most likely the result of its ability to induce the expansion of clones of effector T cells. These studies strongly implicate IL 2 as an important factor in autoimmune diseases in which effector T cells are involved.