Studying the biology of cytotoxic T lymphocytes in vivo with a fluorescent granzyme B-mTFP knock-in mouse

Praneeth Chitirala, Hsin Fang Chang, Paloma Martzloff, Christiane Harenberg, Keerthana Ravichandran, Midhat H. Abdulreda, Per Olof Berggren, Elmar Krause, Claudia Schirra, Trese Leinders-Zufall, Fritz Benseler, Nils Brose, Jens Rettig

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding T cell function in vivo is of key importance for basic and translational immunology alike. To study T cells in vivo, we developed a new knock-in mouse line, which expresses a fusion protein of granzyme B, a key component of cytotoxic granules involved in T cell-mediated target cell-killing, and monomeric teal fluorescent protein from the endogenous Gzmb locus. Homozygous knock-ins, which are viable and fertile, have cytotoxic T lymphocytes with endogeneously fluorescent cytotoxic granules but wild-type-like killing capacity. Expression of the fluorescent fusion protein allows quantitative analyses of cytotoxic granule maturation, transport and fusion in vitro with super-resolution imaging techniques, and two-photon microscopy in living knock-ins enables the visualization of tissue rejection through individual target cell-killing events in vivo. Thus, the new mouse line is an ideal tool to study cytotoxic T lymphocyte biology and to optimize personalized immunotherapy in cancer treatment.

Original languageEnglish (US)
Article numbere58065
Pages (from-to)1-19
Number of pages19
JournaleLife
Volume9
DOIs
StatePublished - Jul 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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