Adequate immune response ensured by binary IL-2 and graded CD25 expression in a murine transfer model
- Robert Koch Institute, Germany
- A Leibniz Institute, Germany
- Charité University Medicine, Germany
Figures
Figure 1 with 6 supplements
Binary IL-2 secretion of adoptively transferred Th cells in vivo after immunization with increasing amounts of antigen and kinetics of IL-2 secretion.
BALB/c mice, adoptively transferred with OVA-specific T cells from DO11.10 mice, were immunized intravenously with the indicated amounts of OVA and 10 μg LPS as adjuvant and analyzed 14 hr later (A–C…
Figure 1—figure supplement 1
The cytokine capture matrix is not saturated by the endogenous IL-2 secretion.
C57BL/6 mice with adoptively transferred sorted naive (CD62Lhi) CD4+ T cells from OT-II mice were immunized intravenously with 2 mg OVA and 10 µg LPS as adjuvant and analyzed at 7 hr. (A) At the end …
Figure 1—figure supplement 2
Binary IL-2 secretion of adoptively transferred OT-II Th cells in vivo after immunization with increasing amounts of antigen.
C57BL/6 mice, adoptively transferred with sorted naive (CD62Lhi) OVA-specific CD4+ T cells from OT-II mice, were immunized intravenously with the indicated amounts of OVA and 10 μg LPS as adjuvant …
Figure 1—figure supplement 3
Confirmation of binary IL-2 expression using Gaussian mixture models.
Mode expression values are extracted as mean values of the components of a fitted Gaussian mixture model taking data of Figure 1, in (B) only 2 mice per group are depicted. Models with two mixture …
Figure 1—figure supplement 4
Transcriptional regulation of IL-2 secretion in adoptively transferred Th cells.
C57BL/6 mice with adoptively transferred sorted naive (CD62Lhi) CD4+ T cells from OT-II mice were immunized intravenously with increasing amounts of OVA and 10 μg LPS as adjuvant and analyzed at 7 …
Figure 1—figure supplement 5
Expression levels of CD25 and CD69 on T cell subpopulations after immunization.
BALB/c mice with adoptively transferred sorted OVA-TCR+ CD4+ T cells from DO11.10 mice were immunized intravenously with increasing amounts of OVA and 10 μg LPS as adjuvant and analyzed at 14 hr. …
Figure 1—figure supplement 6
Expression levels of CD25 on T cell subpopulations at rest and after immunization.
BALB/c mice with adoptively transferred sorted OVA-TCR+ CD4+ T cells from DO11.10 mice were immunized intravenously with 2 mg OVA and 10 μg LPS as adjuvant and anaylzed at 14 hr or left unimmunized. …
Figure 2
In vivo kinetics of IL-2 secretion and CD25 expression in adoptively transferred Th cells after immunization and their correlation upon titration of antigen amount as well as over time.
BALB/c mice, adoptively transferred with OVA-specific T cells from DO11.10 mice, were immunized intravenously with increasing amounts of OVA and 10 μg LPS as adjuvant and analyzed at 14 hr (A) or 2 …
Figure 3 with 1 supplement
Model and experimental validation of binary versus graded IL-2 production.
(A) Schematic representation for the effects of different modes of IL-2 secretion (red) by Th (blue) on surrounding Th (blue) and Treg (green) cells. Graded IL-2 secretion at low antigen dose (left) …
Figure 3—figure supplement 1
Simulation model of binary versus graded IL-2 production.
Model of IL-2 mediated Th and Treg cell activation via CD25. IL-2 producing (P), IL-2 non-producing (N) T helper cells and regulatory T cells (R) are randomly distributed in a grid. The level of …
Figure 4
Treatment of mice with recombinant IL-2 does not increase STAT5 activation.
C57BL/6 mice, adoptively transferred with OVA-specific T cells from OT-II mice, were immunized intravenously with 2000 µg OVA and 10 µg LPS or were left unimmunized. After 12 hr mice received either …
Figure 5 with 1 supplement
Dependency of in vivo proliferation rate of adoptively transferred Th and Treg cells on amount of antigen.
BALB/c mice, adoptively transferred with CFSE-labeled OVA-specific T cells from DO11.10 mice, were immunized intravenously with increasing amounts of OVA and 10 μg LPS as adjuvant and analyzed at 72 …
Figure 5—figure supplement 1
Antigen-specific Treg cells show less apoptosis then conventional Th cells at low amounts of antigen.
BALB/c mice with adoptively transferred sorted OVA-TCR+ CD4+ T cells from DO11.10×DEREG mice were immunized intravenously with increasing amounts of OVA and 10 μg LPS as adjuvant and analyzed at 72 …
Additional files
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Supplementary file 1
Parameter estimates for the mathematical model.
Parameter names, symbols and values used for the mathematical modeling are given.
- https://doi.org/10.7554/eLife.20616.015
