Potential role for perforin (pfp) in immune homeostasis. Mutations in perforin have been shown to be responsible for CD8⁺ T-cell and macrophage hyperplasia, suggesting that immunoregulatory cells (possibly CD8⁺ T cells) use perforin for the suppression of these cells (blunt arrows). In a mouse model of GVHD, in which F1 hybrid animals receive lymphocytes from one of the parental strains (C57BL/6), donor CD4⁺ T cells promote host (shaded) B-cell expansion (pointed arrows). If unchecked, this expansion results in chronic GVHD. In this strain combination, donor CD8⁺ T cells mediate the elimination of the host B cells (blunt arrow) and result in acute GVHD. EBV has been shown to infect B cells and can result in the development of an EBV lymphoma. It is suggested here that CD8⁺ T cells might use the perforin-dependent pathway of target cell killing to suppress the proliferation of such EBV-infected B cells.