CD8+ T cells were previously shown to be important in preventing lymphoproliferation and immunodeficiency following
infection of
murine AIDS (
MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To further evaluate the mechanisms contributing to
MAIDS resistance, we studied mice lacking CD8+ T cells or deficient in
perforin due to knockout of the beta2-microglobulin (beta2M) or
perforin gene, respectively. In contrast to wild-type,
MAIDS-resistant controls, B10.A mice homozygous for the beta2M mutation and B10.D2 mice homozygous for the
perforin mutation were diagnosed as having
MAIDS by 5 to 8 weeks after
infection by the criteria of lymphoproliferation, impaired proliferative responses to
mitogens, and changes in cell populations as judged by histopathology and flow cytometry. Unexpectedly, there was no progression of lymphoproliferation through 24 weeks, even though immune functions were severely compromised. Expression of the defective virus responsible for
MAIDS was enhanced in spleens of the knockouts in comparison with wild-type mice. These results demonstrate that
perforin-dependent functions of CD8+ T cells contribute to
MAIDS resistance but that other, non-CD8-dependent mechanisms are of equal or greater importance.