Murine AIDS is an antigen-driven disease: requirements for major histocompatibility complex class II expression and CD4+ T cells.
Murine AIDS (MAIDS) is a complex syndrome of lymphoproliferation and immunodeficiency induced by a replication-defective murine leukemia virus (BM5def) that encodes Pr60gag as its only product. It has been suggested 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 required for presentation of antigens to CD4+ T cells. C2K/O mice expressed BM5def at high levels but did not develop MAIDS either when unmanipulated or following transfer of CD4+ T cells. Second, B6 mice reconstituted with C2K/O bone marrow cells had normal frequencies of B cells (class II negative) and CD4+ cells and expressed high levels of BM5def transcripts but did not develop MAIDS; however, MAIDS developed in 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-positive B cells and with purified CD4+ T cells. These results indicate that 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.
Giese
N A
NA
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Giese
T
T
Morse
H C
HC
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009052:Leukemia Virus, Murine / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens