Mixed leukocyte reaction in rats. Effect of immunization with bovine encephalitogenic protein and Freund's complete...

Rats of certain strains immunized with bovine encephalitogenic protein (EP) in Freund's complete adjuvant develop an impairment of the mixed leukocyte reaction (MLR) similar to that seen in rabbits with experimental autoimmune encephalomyelitis and in humans with certain diseases, including multiple sclerosis. The rats mount a cell-bound response to EP, but encephalomyelitis does not develop. The component causing the impairment was analysed in a culture system using inbred rat strains and F1 hybrids, thoracic duct cells as a source of lymphocytes, and blood as a supplement to the cultures. In normal rats, it was shown that the effects of responding and of stimulating lymphocytes could be separated and that the supportive action of the added blood was probably due to macrophages (monocytes); also that the added blood could in many experiments be replaced with 2-mercaptoethanol (2-ME). The impairment present in immunized rats is at least largely due to a defective supportive activity of the blood (monocytes) and can be restored with 2-ME. The results argue that the MLR impairment seen in immunized rats is due to a faulty macrophage function.