Expression of Mtv-7 sag gene in vivo using a retroviral vector results in selective inactivation of superantigen reactive T cells.
T cells expressing specific TCR V beta chains are intrathymically eliminated in mice expressing the murine Mls (minor lymphocyte stimulating) superantigens. Recently, in vitro studies have shown that the endogenous mouse mammary tumor virus (MMTV)-7 sag gene encodes Mls-1 Ag. The demonstrated ability of MMTV superantigen proteins to react with TCRs has led to the postulate that other infectious retroviruses may use superantigen-like molecules to modify the host's immune system. In this report, successful retrovirus-mediated Mtv-7 sag gene transfer into pluripotent hematopoietic stem cells is described. In two different strains of Mls-1- host mice (CBA/Ca and BALB/c) reconstituted with Mtv-7 sag gene expressing bone marrow cells, low levels of ectopic Mtv-7 sag gene expression on syngeneic donor hematopoietic stem cell-derived population alone can induce partial clonal deletion of Mls-1 reactive V beta 6+ and V beta 8.1+ T cells, and complete clonal inactivation of V beta 8.1+ T cells.
Kang
J
J
Division of Molecular Immunology and Neurobiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Ido
E
E
Pawling
J
J
Beutner
U
U
Huber
B T
BT
Hozumi
N
N
D000818:Animals; D001483:Base Sequence; D017635:Clonal Anergy; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D012190:Retroviridae; D018089:Superantigens / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D017931:DNA Primers; D016747:Minor Lymphocyte Stimulatory Antigens; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens