@article {542266,
	title = {CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition.},
	journal = {J Immunol},
	volume = {186},
	number = {3},
	year = {2011},
	month = {2011 Feb 1},
	pages = {1598-607},
	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 = {Aerosols, Animals, Antigens, CD274, Antigens, CD80, Antigens, Surface, Apoptosis Regulatory Proteins, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Genetic Predisposition to Disease, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Mycobacterium tuberculosis, Necrosis, Peptides, Programmed Cell Death 1 Receptor, Tuberculosis, Pulmonary},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1003304},
	author = {Barber, Daniel L and Mayer-Barber, Katrin D and Feng, Carl G and Sharpe, Arlene H and Sher, Alan}
}
