title: A gamma interferon independent mechanism of CD4 T cell mediated control of M. tuberculosis infection in vivo.
abstract: CD4 T cell deficiency or defective IFNγ signaling render humans and mice highly susceptible to Mycobacterium tuberculosis (Mtb) infection. The prevailing model is that Th1 CD4 T cells produce IFNγ to activate bactericidal effector mechanisms of infected macrophages. Here we test this model by directly interrogating the effector functions of Th1 CD4 T cells required to control Mtb in vivo. While Th1 CD4 T cells specific for the Mtb antigen ESAT-6 restrict in vivo Mtb growth, this inhibition is independent of IFNγ or TNF and does not require the perforin or FAS effector pathways. Adoptive transfer of Th17 CD4 T cells specific for ESAT-6 partially inhibited Mtb growth while Th2 CD4 T cells were largely ineffective. These results imply a previously unrecognized IFNγ/TNF independent pathway that efficiently controls Mtb and suggest that optimization of this alternative effector function may provide new therapeutic avenues to combat Mtb through vaccination.
authors.affiliation: NIH/NIAID Laboratory of Parasitic Diseases, Bethesda, Maryland, United States of America.
authors.forename: Alena M
authors.initials: AM
authors.lastname: Gallegos
authors.forename: Jeroen W J
authors.initials: JW
authors.lastname: van Heijst
authors.forename: Miriam
authors.initials: M
authors.lastname: Samstein
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Su
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Glickman
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D053222:Fas Ligand Protein / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D054353:Perforin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D053222:Fas Ligand Protein; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II