Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells

PLoS One. 2016 Aug 23;11(8):e0161505. doi: 10.1371/journal.pone.0161505. eCollection 2016.


Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either anti-CD3/CD28 or Concanavalin A, but, as predicted, were completely unresponsive to IL-1β administration. Furthermore, IL-1R1ΔT mice were protected from gut inflammation in the anti-CD3 treatment model, due to dramatically reduced frequencies and absolute numbers of IL-17A and interferon (IFN)-γ producing cells. Taken together, our data shows the necessity of intact IL-1 signaling for survival and expansion of CD4 T cells that were developed in an otherwise IL-1 sufficient environment.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • B-Lymphocytes / metabolism
  • Biomarkers
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Proliferation
  • Cell Survival / genetics*
  • Cytokines / biosynthesis*
  • Gene Targeting
  • Immunophenotyping
  • Interleukin-1 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • Receptors, Interleukin-1 Type I / deficiency*
  • Receptors, Interleukin-1 Type I / genetics
  • Signal Transduction
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*


  • Antibodies, Monoclonal
  • Biomarkers
  • CD3 Complex
  • Cytokines
  • Interleukin-1
  • Interleukin-1beta
  • Receptors, Interleukin-1 Type I