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J Immunol. 2019 Sep 23. pii: ji1900075. doi: 10.4049/jimmunol.1900075. [Epub ahead of print]

In Vivo Function of the Lipid Raft Protein Flotillin-1 during CD8+ T Cell-Mediated Host Surveillance.

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Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland.
Department for Infectious Diseases, Integrative Virology, Center for Integrative Infectious Disease Research, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Biotechnology Institute Thurgau at the University of Konstanz, 8280 Kreuzlingen, Switzerland.
Scientific Institute for Research and Healthcare, San Raffaele Scientific Institute, 20132 Milan, Italy.
Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland.
Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany; and.
Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland;


Flotillin-1 (Flot1) is an evolutionary conserved, ubiquitously expressed lipid raft-associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired because of a decrease in myosin II-mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. In this study, we analyzed morphology and migration parameters of murine wild-type and Flot1-/- CD8+ T cells using in vitro assays and intravital two-photon microscopy of lymphoid and nonlymphoid tissues. Flot1-/- CD8+ T cells displayed significant alterations in cell shape and motility parameters in vivo but showed comparable homing to lymphoid organs and intact in vitro migration to chemokines. Furthermore, their clonal expansion and infiltration into nonlymphoid tissues during primary and secondary antiviral immune responses was comparable to wild-type CD8+ T cells. Taken together, Flot1 plays a detectable but unexpectedly minor role for CD8+ T cell behavior under physiological conditions.


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