CONTROL OF IMMUNODEFICIENCY AND LYMPHOPROLIFERATION IN MOUSE AIDS - STUDIES OF MICE DEFICIENT IN CD8(-CELLS OR PERFORIN() T)

CD8(+) T cells were previously shown to be important in preventing lym phoproliferation and immunodeficiency following infection of murine AI DS (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia v iruses. To further evaluate the mechanisms contributing to MAIDS resis tance, we studied mice lacking CD8(+) T cells or deficient in perforin due to knockout of the beta 2-microglobulin (beta 2M) or perforin gen e, respectively, In contrast to wild-type, MAIDS-resistant controls, B 10.A mice homozygous for the beta 2M mutation and B10.D2 mice homozygo us for the perforin mutation were diagnosed as having MAIDS by 5 to 8 weeks after infection bg the criteria of lymphoproliferation, impaired proliferative responses to mitogens, and changes in cell populations as judged by histopathology and flow cytometry. Unexpectedly, there wa s no progression of lymphoproliferation through 24 weeks, even though immune functions were severely compromised. Expression of the defectiv e virus responsible for MAIDS was enhanced in spleens of the knockouts in comparison with wild-type mice. These results demonstrate that per forin-dependent functions of CD8(+) T cells contribute to MAIDS resist ance but that other, non-CD8-dependent mechanisms are of equal or grea ter importance.