title: Control of chronic mycobacterium tuberculosis infection by CD4 KLRG1- IL-2-secreting central memory cells.
abstract: The bacille Calmette-Guérin vaccine provides very efficient protection in standard animal models of Mycobacterium tuberculosis challenge. We show in this article that although bacille Calmette-Guérin controlled M. tuberculosis growth for 7 wk of infection, the protection was gradually lost as the infection entered the chronic phase. The regrowth of M. tuberculosis coincided with an almost complete disappearance of IL-2-producing CD4 T cells. Booster vaccination with a subunit vaccine (Ag85B-ESAT-6+CAF01) expanded IL-2(+) CD4(+) T cell coexpressing either TNF-α or TNF-α/IFN-γ, and the maintenance of this population in the late stage of infection was associated with enhanced control of bacterial growth. The IL-2(+) CD4(+) T cell subsets were KLRG1(-) (nonterminally differentiated), were found to be CD62L(high), and further maintained a pronounced proliferative and cytokine-producing potential in the draining lymph nodes, when the animals were challenged 2 y postvaccination. These results suggest that the CD4(+) KLRG1(-) IL-2-secreting subsets are central memory T cells with the potential to continuously replenish the T cells at the site of infection and prevent attrition and functional exhaustion.
authors.affiliation: Tuberculosis Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lindenstrøm
authors.forename: Niels Peter Hell
authors.initials: NP
authors.lastname: Knudsen
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control
chemical_list: D001500:BCG Vaccine; D007376:Interleukin-2; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic