Local secretion of a chimeric anti-CD4 antibody protects against graft rejection in the NOD mouse.
BACKGROUND
Engineering a graft to secrete its own immunosuppressive antibodies may minimize the risks associated with current high dose systemic immunosuppression.


RESULTS
A beta cell insulinoma cell line (NIT-1) was transfected with genes encoding a chimeric anti-CD4 antibody. The NIT-1 cells secreted functional chimeric anti-CD4 antibody that bound to the CD4 molecule on mouse thymocytes and inhibited in vitro proliferation of CD4+ve T cells. Both test and control transfected cell lines grew at a similar rate in immunodeficient mice. In immunocompetent NOD mice, NIT-1 cells are normally rejected by a cellular immune response against the SV40 T antigen. Although control transfected NIT-1 cells were rapidly rejected by NOD mice, anti-CD4 secreting NIT-1 cells grew significantly better and were able to form tumors at the site of injection.


CONCLUSIONS
The local secretion of chimeric anti-CD4 antibody from transfected cells can contribute to graft survival in our transplantation model.
McKenzie
A W
AW
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Brady
J L
JL
Martin
R M
RM
Georgiou
H M
HM
Lew
A M
AM
D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000378:metabolism*; D015704:CD4 Antigens / Q000276:immunology*; D002678:Chimera; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015704:CD4 Antigens