Elevated IL-7 availability does not account for T cell proliferation in moderate lymphopenia

Area of Science:

• Immunology
• T cell biology
• Cellular proliferation

Background:

• Lymphopenia-induced proliferation (LIP) is a T cell response to immune depletion.
• Interleukin-7 (IL-7) and T cell receptor (TCR) signaling are known critical factors for LIP.

Purpose of the Study:

• To investigate the impact of IL-7 and TCR signaling on T cell proliferation in moderately lymphopenic environments.
• To compare T cell proliferation in moderate versus severe lymphopenia.

Main Methods:

• Transferring T cells into IL-7Rα knock-in mutant (IL-7Rα(449F)) mice with moderate lymphopenia.
• Comparing proliferation kinetics and TCR repertoire diversity with cells transferred into IL-7Rα(-/-) mice with severe lymphopenia.
• Assessing IL-7 availability and self-peptide-MHC interactions.

Main Results:

• Moderate lymphopenia in IL-7Rα(449F) mice supported T cell proliferation, but with reduced frequency and kinetics compared to severe lymphopenia.
• Elevated IL-7 levels were not observed in moderately lymphopenic mice.
• Moderate lymphopenia enhanced T cell access to self-peptide presented on APCs, triggering TCR signaling and proliferation.
• Proliferated T cells maintained a diverse TCR repertoire in both moderate and severe lymphopenic conditions.

Conclusions:

• Polyclonal T cells can proliferate through self-peptide-MHC interaction alone or with IL-7, retaining TCR diversity.
• T cell reconstitution is most effective when IL-7 availability is increased.
• Moderate lymphopenia can drive T cell proliferation via TCR signaling, independent of elevated IL-7 levels.