In perforin-deficient mice infected with high doses of lymphocytic choriomeningitis virus (LMCV), haemophagocytic lymphohistiocytosis could be induced, similar to human FHL [18] . This suggests that failure to clear virus will lead to persistence of viral antigens and prolonged CD8 T cell activation and cytokine production. Other animal model studies demonstrate perforin's role in regulating lymphocyte number in autoimmunity [19] , after microbial infection [20] and when other cell-death pathways are impaired [21] . The extent that these mechanisms are involved in the control of immune responses, however, is still speculative.