PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice

• Type of Material: Article
• Authors: Scott N. Mueller, University of Melbourne; Vijay K. Vanguri, Emory University; Sang-Jun Ha, Emory University; Erin E. West, Emory University; Mary E. Keir, Emory University; Jonathan N. Glickman, Emory University; Arlene H. Sharpe, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2010-07-01
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2010, American Society for Clinical Investigation
• Final Published Version (URL): http://www.jci.org/120/7
• Title of Journal or Parent Work: Journal of Clinical Investigation
• ISSN: 0021-9738
• Volume: 120
• Issue: 7
• Start Page: 2508
• End Page: 2515
• Grant/Funding Information: T32 HL007627 to Brigham and Women’s Hospital for V.K. Vanguri), and grants from the Gates Foundation Grand Challenges in Global Health to R. Ahmed, and the Korean Health Technology R&D project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A091204 to S.-J. Ha).; AI30048 and AI04464409 to R. Ahmed; This work was supported by grants from the NIH (AI56299 to A.H. Sharpe and R. Ahmed
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

The inhibitory receptor programmed death 1 (PD-1) is upregulated on antigen-specific CD8+ T cells during persistent viral infections. Interaction with PD-1 ligand 1 (PD-L1) contributes to functional exhaustion of responding T cells and may limit immunopathology during infection. PD-L1 is expressed on both hematopoietic and nonhematopoietic cells in tissues. However, the exact roles of PD-L1 on hematopoietic versus nonhematopoietic cells in modulating immune responses are unclear. Here we used bone marrow chimeric mice to examine the effects of PD-L1 deficiency in hematopoietic or nonhematopoietic cells during lymphocytic choriomeningitis virus clone 13 (LCMV CL-13) infection. We found that PD-L1 expression on hematopoietic cells inhibited CD8+ T cell numbers and function after LCMV CL-13 infection. In contrast, PD-L1 expression on nonhematopoietic cells limited viral clearance and immunopathology in infected tissues. Together, these data demonstrate that there are distinct roles for PD-L1 on hematopoietic and nonhematopoietic cells in regulating CD8+ T cell responses and viral clearance during chronic viral infection.