CD4 T Cells Promote Rather than Control Tuberculosis in the Absence of PD-1–Mediated Inhibition
- 1 February 2011
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 186 (3), 1598-1607
- https://doi.org/10.4049/jimmunol.1003304
Abstract
Although CD4 T cells are required for host resistance to Mycobacterium tuberculosis, they may also contribute to pathology. In this study, we examine the role of the inhibitory receptor PD-1 and its ligand PD-L1 during M. tuberculosis infection. After aerosol exposure, PD-1 knockout (KO) mice develop high numbers of M. tuberculosis-specific CD4 T cells but display markedly increased susceptibility to infection. Importantly, we show that CD4 T cells themselves drive the increased bacterial loads and pathology seen in infected PD-1 KO mice, and PD-1 deficiency in CD4 T cells is sufficient to trigger early mortality. PD-L1 KO mice also display enhanced albeit less severe susceptibility, indicating that T cells are regulated by multiple PD ligands during M. tuberculosis infection. M. tuberculosis-specific CD8 T cell responses were normal in PD-1 KO mice, and CD8 T cells only had a minor contribution to the exacerbated disease in the M. tuberculosis-infected PD-1 KO and PD-L1 KO mice. Thus, in the absence of the PD-1 pathway, M. tuberculosis benefits from CD4 T cell responses, and host resistance requires inhibition by PD-1 to prevent T cell-driven exacerbation of the infection.Keywords
This publication has 53 references indexed in Scilit:
- Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy?Nature Reviews Microbiology, 2010
- Programmed death-1 (PD-1)–deficient mice are extraordinarily sensitive to tuberculosisProceedings of the National Academy of Sciences of the United States of America, 2010
- Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosisThe Journal of Experimental Medicine, 2010
- Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconservedNature Genetics, 2010
- Memory CD4+ T cells induce innate responses independently of pathogenNature Medicine, 2010
- Contrasting persistence strategies in Salmonella and MycobacteriumCurrent Opinion in Microbiology, 2010
- Enhancing SIV-specific immunity in vivo by PD-1 blockadeNature, 2008
- The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungusHistoplasma capsulatumProceedings of the National Academy of Sciences of the United States of America, 2008
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infectionThe Journal of Experimental Medicine, 2006