Induction of autoantibodies to different interleukin-2 allotypes

We report the development of an in vivo system to induce the generation, and study the potential role, of autoantibodies to the lymphokine interleukin-2 (IL-2). To elicit IL-2 autoantibodies, mice were immunized with purified fusion proteins containing the N-terminal region of different IL-2 allotypes, where major changes have been observed. This part of the IL-2 molecule includes a conserved sequence with an essential residue for interacting with the beta-chain of the heterotrimeric IL-2 receptor. Mice bearing an RF IL-2 allotype, immunized with several N-terminal IL-2 fusion proteins, produced IgG antibodies against Mus musculus, C57BL/6, Mus spretus and the self molecule RF IL-2, but there were large differences among then in reactivity. These N-terminal IL-2 immunogens break the maintenance of self tolerance possibly by the introduction of new T cell epitopes on self IL-2. The immunized mice developed a complex set of immunopathologies such as splenomegaly, haemolytic anaemia and lymphoadenopathy with a long latency period after the last immunization. These pathologies resembled those described for IL-2-deficient mice (IL-2(-/-)) and mice injected with anti-IL-2 receptor alpha-antibody. Human IL-2 autoantibodies have been detected in several immune-affected situations and therefore this model would be of interest to study the potential evolution of these autoantibodies in relation to immunopathology. The production of these autoantibodies against conserved epitopes of mouse IL-2 may facilitate studies on the structural homologies between different IL-2 allotypes and from various species, and could be applied to other cytokines.