Overall, the novel regulatory effects shown by agonistic 4-1BB ligands on modulation of potentially dangerous responses of CD4+ T cells specific for Ag85B - an antigen actively secreted by replicating MTB and proposed as a candidate sub-unit TB vaccine - open novel strategies for intervention in TB pathology and vaccination through T-cell co-stimulatory-based molecular targeting. This evidence concerns the gene TNFRSF9 and tuberculosis.