MURINE AIDS IS AN ANTIGEN-DRIVEN DISEASE - REQUIREMENTS FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION AND CD4-CELLS( T)

Murine AIDS (MAIDS) is a complex syndrome of lymphoproliferation and i mmunodeficiency induced by a replication-defective murine leukemia vir us (BM5def) that encodes Pr60(gag) as its only product. It has been su ggested that the gag polyprotein is responsible for vigorous antigenic stimulation of CD4(+) T cells and generalized secondary activation of the immune system. This model was tested first by infecting mice (C2K /O) that lack class II major histocompatibility complex molecules requ ired for presentation of antigens to CD4(+) T cells. C2K/O mice expres sed BM5def at high levels but did not develop MAIDS either when unmani pulated or following transfer of CD4(+) T cells. Second, B6 mice recon stituted with C2K/O bone marrow cells had normal frequencies of B cell s (class II negative) and CD4(+) cells and expressed high levels of BM 5def transcripts but did not develop MAIDS; however, MAIDS developed i n class II-competent nu/nu mice reconstituted with CD4(+) T cells and in C2K/O mice reconstituted with B6 bone marrow to give class II-posit ive B cells and with purified CD4(+) T cells. These results indicate t hat induction of MAIDS by BM5def is antigen driven and is dependent on expression of major histocompatibility complex class II molecules on antigen-presenting cells and the presence of CD4(+) T cells.