Galectin-3 Regulates γ-Herpesvirus Specific CD8 T Cell Immunity

Manpreet Kaur; Dhaneshwar Kumar; Vincent Butty; Sudhakar Singh; Alexandre Esteban; Gerald R Fink; Hidde L Ploegh; Sharvan Sehrawat

doi:10.1016/j.isci.2018.10.013

Galectin-3 Regulates γ-Herpesvirus Specific CD8 T Cell Immunity

iScience. 2018 Nov 30:9:101-119. doi: 10.1016/j.isci.2018.10.013. Epub 2018 Oct 17.

Authors

Manpreet Kaur¹, Dhaneshwar Kumar¹, Vincent Butty², Sudhakar Singh¹, Alexandre Esteban², Gerald R Fink², Hidde L Ploegh³, Sharvan Sehrawat⁴

Affiliations

¹ Indian Institute of Science Education and Research Mohali, Sector 81 SAS Nagar, PO Manauli, Mohali, Knowledge City 140306, Punjab, India.
² Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge 02142 MA, USA.
³ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge 02142 MA, USA. Electronic address: hidde.ploegh@childrens.harvard.edu.
⁴ Indian Institute of Science Education and Research Mohali, Sector 81 SAS Nagar, PO Manauli, Mohali, Knowledge City 140306, Punjab, India. Electronic address: sharvan@iisermohali.ac.in.

Abstract

To gain insights into the molecular mechanisms and pathways involved in the activation of γ-herpesvirus (MHV68)-specific T cell receptor transnuclear (TN) CD8⁺ T cells, we performed a comprehensive transcriptomic analysis. Upon viral infection, we observed differential expression of several thousand transcripts encompassing various networks and pathways in activated TN cells compared with their naive counterparts. Activated cells highly upregulated galectin-3. We therefore explored the role of galectin-3 in influencing anti-MHV68 immunity. Galectin-3 was recruited at the immunological synapse during activation of CD8⁺ T cells and helped constrain their activation. The localization of galectin-3 to immune synapse was evident during the activation of both naive and memory CD8⁺ T cells. Galectin-3 knockout mice mounted a stronger MHV68-specific CD8⁺ T cell response to the majority of viral epitopes and led to better viral control. Targeting intracellular galectin-3 in CD8⁺ T cells may therefore serve to enhance response to efficiently control infections.

Keywords: Immune Response; Immunology; Transcriptomics; Virology.