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

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 di...

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Published inbioRxiv
Main Authors Mullins, Genevieve N, Valentine, Kristen M, Al-Kuhlani, Mufadhal, Davini, Dan, Jensen, Kirk Dc, Hoyer, Katrina K
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.06.2018
Subjects
Anemia
Autoimmune diseases
Autoimmune hemolytic anemia
Bone marrow
CD4 antigen
CD8 antigen
Cell activation
Hematocrit
Hemolytic anemia
Hemopoiesis
Immunological memory
Interleukin 2
Interleukin 2 receptors
Lymphocytes T
Memory cells
Peripheral blood
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Summary: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-2R 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