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

Genevieve N Mullins, Kristen M Valentine, Mufadhal Al-Kuhlani, Dan Davini, Kirk D.C. Jensen, Katrina K Hoyer
2018 bioRxiv   pre-print
IL-2Rα is required to generate the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. Mice deficient in IL-2Rα (IL-2Rα-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
more » ... velop early- and late-stage autoimmune disease in the IL-2Rα-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-2Rα-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-2Rα-KO mice is driven by unimpaired IL-2 signaling which correlated with increased IL-2Rβ expression. Using a simple CBC count we were able to predict disease kinetics to explore mechanisms underlying early and late disease.
doi:10.1101/345512 fatcat:nijggunopnbc3ckdadohknzbiq