In general, the excessive triggering of costimulatory molecules, including CD28, CD27, and 4-1BB, resulted in detrimental effects, particularly on B cells, via IFN-γ-producing T cells.27,34,35 Our data further demonstrate that chronic activation of 4-1BB has detrimental effects on the immune system by inducing the development of granulomas in TDLNs. This evidence concerns the gene TNFRSF9 and Granuloma.