In addition to their role as effector cells in virus control, natural killer (NK) cells have an immunoregulatory function in shaping the
antiviral T-cell response. This function is further pronounced in
perforin-deficient mice that show the enhanced NK-cell proliferation and
cytokine secretion upon mouse cytomegalovirus (MCMV)
infection. Here, we confirmed that stronger activation and maturation of NK cells in
perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of
perforin, we compared the response of NK cells that express or do not express
perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of
perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that
perforin plays an intrinsic role as a feedback mechanism in the regulation of NK-cell proliferation during
viral infections.