Oral Presentations: Basic Sciences II.
Dr. Bencsik, András
Semmelweis University, Department of Genetics, Cell- and Immunobiology
+36 1 210 2930/56107
bencsikandras89@gmail.com
Explorative analysis of the dynamics of the murine CD103+ cytotoxic resident memory T cell responses during influenza reinfection
András Bencsik1,2, Barbara Érsek1,2, Nikolett Lupsa1,2, István Jankovics3, János Matkó4, Edit Irén Buzás2, Zoltán Pós1,2
1 Experimental and Translational Immunomics Research Group, Budapest
2 Semmelweis University, Department of Genetics, Cell and Immunobiology, Budapest
3 National Center for Epidemiology, Division of Virology, Budapest
4 Eötvös Loránd University, Department of Immunology, Budapest
molecular sciences
Oral Presentations: Basic Sciences II.
Doctoral School: Molecular Medicine
Program: Basis of Human Molecular Genetics and Gene Diagnostics
Supervisor: Zoltán Pós
E-mail address: bencsikandras89@gmail.com
CD8+ resident memory T cells (Trm) are sentinel-like memory cells maintaining an early warning system and also constituting the first line of defense against various recurring viral infections in diverse tissues. Nonetheless, the exact contribution of CD8+ Trm cells to recall antiviral immune responses is still elusive, in part because it seems to be fine-tuned by both the viral entity in question, and local tissue environs.
This study aims at a better understanding of the earliest response mechanisms initiated by lung-resident murine CD8+ Trm cells activated by influenza reinfection in vivo.
Lung resident CD8+ Trm cells were generated in naïve C57Bl/6J mice by intranasal infection using sublethal dose (150xTCID50) of mouse-adapted influenza A/PR/8/34 (H1N1), and subsequently activated by lethal dose viral challenge (150.000xTCID50) six weeks later. Successful viral infection was confirmed by monitoring weight loss, performing lung histology, and influenza-specific immunohistochemistry. Next, lungs were subjected to automated tissue dissociation using a GentleMACS Octo platform, and establishment of virus-specific CD8+ resident memory was validated by enumerating nucleoprotein-specific Trm cells with MHC tetramer staining. Finally, live CD8b+CD69+CD103hi (Trm) cells were FACS-sorted from dissociated lungs, harvested on days 0, 1, 2, and 3 after reinfection. Isolated CD8+ Trm cells were analyzed by transcriptome profiling and flow cytometry. CD8+ Trm-specific changes were identified by using pulmonary non-resident CD8+ T cells as reference.
Preliminary findings suggest that influenza-induced expression of several transcription factors, chemokine receptors and metalloproteases is restricted to the CD8+ Trm subset during influenza re-infection.
These data suggest that a systematic comparison of the dynamics of CD8+ Trm and non-Trm responses may disclose previously hidden aspects of the activity of tissue-resident memory cells in recurrent viral infections.
Szabad
nem rendelkezett róla
1275
András Bencsik1,2, Barbara Érsek1,2, Nikolett Lupsa1,2, István Jankovics3, János Matkó4, Edit Irén Buzás2, Zoltán Pós1,2
1 Experimental and Translational Immunomics Research Group, Budapest
2 Semmelweis University, Department of Genetics, Cell and Immunobiology, Budapest
3 National Center for Epidemiology, Division of Virology, Budapest
4 Eötvös Loránd University, Department of Immunology, Budapest