Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells.


Humans and mice with impaired perforin-dependent cytotoxic function may develop excessive T-cell activation and the fatal disorder hemophagocytic lymphohistiocytosis (HLH) after infection. Though cytotoxic lymphocytes can kill antigen-presenting cells, the physiological mechanism of perforin-mediated immune regulation has never been demonstrated in a disease-relevant context. We used a murine model of HLH to examine how perforin controls immune activation, and we have defined a feedback loop that is critical for immune homeostasis. This endogenous feedback loop involves perforin-dependent elimination of rare, antigen-presenting dendritic cells (DCs) by CD8(+) T cells and has a dominant influence on the magnitude of T-cell activation after viral infection. Antigen presentation by a minor fraction of DCs persisted in T-cell- or perforin-deficient animals and continued to drive T-cell activation well beyond initial priming in the latter animals. Depletion of DCs or transfer of perforin-sufficient T cells dampened endogenous DC antigen presentation and T-cell activation, demonstrating a reciprocal relationship between perforin in CD8(+) T cells and DC function. Thus, selective cytotoxic "pruning" of DC populations by CD8(+) T cells limits T-cell activation and protects against the development of HLH and potentially other immunopathological conditions.

DOI: 10.1182/blood-2013-04-495309

7 Figures and Tables

Citations per Year

64 Citations

Semantic Scholar estimates that this publication has 64 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Terrell2013PerforinDI, title={Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells.}, author={Catherine E. Terrell and Michael B. Jordan}, journal={Blood}, year={2013}, volume={121 26}, pages={5184-91} }