LAG-3- and CXCR5-expressing CD4 T cells display progenitor-like properties during chronic visceral leishmaniasis
Sharada Swaminathan,
Linh Thuy Mai,
Alexandre P. Meli,
Liseth Carmona-Pérez,
Tania Charpentier,
Alain Lamarre,
Irah L. King,
Simona Stäger
Affiliations
Sharada Swaminathan
INRS-Centre Armand-Frappier Santé Biotechnologie and Infectiopôle INRS, 531 Boulevard des Prairies, Laval, QC, Canada
Linh Thuy Mai
INRS-Centre Armand-Frappier Santé Biotechnologie and Infectiopôle INRS, 531 Boulevard des Prairies, Laval, QC, Canada
Alexandre P. Meli
Department of Microbiology & Immunology, Research Institute of the McGill University Health Centre, Meakins-Christie Laboratories, McGill Centre for Microbiome Research, McGill University, Montreal, QC, Canada
Liseth Carmona-Pérez
INRS-Centre Armand-Frappier Santé Biotechnologie and Infectiopôle INRS, 531 Boulevard des Prairies, Laval, QC, Canada
Tania Charpentier
INRS-Centre Armand-Frappier Santé Biotechnologie and Infectiopôle INRS, 531 Boulevard des Prairies, Laval, QC, Canada
Alain Lamarre
INRS-Centre Armand-Frappier Santé Biotechnologie and Infectiopôle INRS, 531 Boulevard des Prairies, Laval, QC, Canada
Irah L. King
Department of Microbiology & Immunology, Research Institute of the McGill University Health Centre, Meakins-Christie Laboratories, McGill Centre for Microbiome Research, McGill University, Montreal, QC, Canada
Simona Stäger
INRS-Centre Armand-Frappier Santé Biotechnologie and Infectiopôle INRS, 531 Boulevard des Prairies, Laval, QC, Canada; Corresponding author
Summary: Maintenance of CD4 T cells during chronic infections is vital for limiting pathogen burden and disease recrudescence. Although inhibitory receptor expression by CD4 T cells is commonly associated with immune suppression and exhaustion, such cell-intrinsic mechanisms that control activation are also associated with cell survival. Using a mouse model of visceral leishmaniasis (VL), we discovered a subset of lymphocyte activation gene 3 (LAG-3)-expressing CD4 T cells that co-express CXCR5. Although LAG3+CXCR5+ CD4 T cells are present in naive mice, they expand during VL. These cells express gene signatures associated with self-renewal capacity, suggesting progenitor-like properties. When transferred into Rag1−/− mice, these LAG3+CXCR5+ CD4 T cells differentiated into multiple effector types upon Leishmania donovani infection. The transcriptional repressor B cell lymphoma-6 was partially required for their maintenance. Altogether, we propose that the LAG3+CXCR5+ CD4 T cell subset could play a role in maintaining CD4 T cell responses during persistent infections.
