T cell and peripheral blood parameters define progression of autoimmune disease in the IL-2Rα KO model

Abstract

IL-2R is required to generate the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. Mice deficient in IL-2R (IL-2R-KO) develop systemic autoimmune disease and die from severe anemia between 18-80 days of age. These mice develop kinetically differing autoimmune disease, with approximately a quarter dying by 21 days of age and half dying after 30 days. This research aims to define immune parameters that distinguish cohorts of mice that develop early- and late-stage autoimmune disease in the IL-2R-KO genetic background. To investigate these differences, we evaluated complete blood counts (CBC), antibody binding of RBCs, T cell numbers and activation, and hematopoietic progenitor changes, to assess the extent of peripheral autoimmune hemolytic anemia and bone marrow failure. Early onset disease correlated with anti-RBC antibodies and lower hematocrit on day 19. We also found that predicted late stage-disease IL-2R-KO mice have higher numbers of developing memory CD4 and CD8 T cells and reduced AIHA at early ages. The expansion of CD8 T cells seen in IL-2R -KO mice is driven by unimpaired IL-2 signaling which correlated with increased IL-2RP expression. Using a simple CBC we were able to predict disease kinetics to explore mechanisms underlying early and late disease.