NKT Cells regulate CTL Cross-priming via a Negative Feedback Loop

New publication in The Journal of Immunology

NKT cells are unconventional T cells whose biological role is only partially understood. Activated NKT cells can cause dendritic cell maturation, which is required for effective CTL responses. However, analyzing their impact on immune responses over time has so far been hindered by the fact that techniques conditionally depleting NKT cells in vivo were missing.
A study lead by Dr Christoph Heuser-Loy, Dr Ann-Kathrin Baumgart and Prof Christian Kurts from the IMMEI and now published in the Journal of Immunology presents two approaches, mixed bone marrow chimeras and a genetic system based on the innate-like lymphocyte transcription factor PLZF, to conditionally deplete NKT cells in vivo. Surprisingly, with these two approaches, a negative feedback loop was observed that regulates alternative cross-priming downstream of dendritic cell maturation. NKT cell depletion after initial DC activation augmented CD8 T cell expansion and cytotoxicity by mechanisms distinct from reduced STAT6 signaling. Further studies are now needed to understand this so far hidden immunoregulatory mechanism in detail.

Heuser-Loy C, Baumgart AK, Hackstein CP, Courrèges CJF, Philipp MS, Thaiss CA, Holland T, Evaristo C, Garbi N, Kurts C:
Conditional NKT Cell Depletion in Mice Reveals a Negative Feedback Loop That Regulates CTL Cross-Priming.
J. Immunol. 2023, ji2300662. https://doi.org/10.4049/jimmunol.2300662.