Antigen-specific drug-targeting used to manipulate an immune response in vivo.
AUTOR(ES)
Abu-hadid, M M
RESUMO
The administration of dextran-conjugated cytosine arabinonucleoside (araC) to BALB/c mice at various times prior to but not subsequent to immunization with native dextran renders mice unresponsive to this thymic-independent antigen. These results demonstrate that the primary immune response to an antigen can be selectively and efficiently suppressed or eliminated in vivo by the delivery of a single dose of an appropriate antigen-cytotoxic drug conjugate. Evidence presented here indicates that the dextran-araC conjugate (toxogen) acts directly and selectively upon unprimed dextran-specific antibody-forming cell precursors, presumably by binding to their receptors and subsequent internalization of the resultant receptor-toxogen complexes. The resistance of antigen-primed mice to the cytotoxic effect of the toxogen could result from the failure of dextran-primed cells to reexpress antigen-specific receptors, from an alternative processing of the toxogen, or from the inability of the antigen-primed cells to internalize a second round of receptor-ligand complexes. We also determined that B cells responding to thymic-dependent antigens were not affected by the prior exposure to a toxogen. The inability to eliminate or suppress the primary response to a thymic-dependent antigen via the administration of a cytotoxic drug-antigen conjugate distinguishes the thymic-independent set of B cells from the thymic-dependent B-cell repertoire. The difference between these two B-cell compartments could be due either to differences in the amount of ligand bound to receptors or to differences in the trafficking patterns of receptor-ligand complexes within each cell type.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=299265Documentos Relacionados
- Achieving antigen-specific immune regulation
- Messenger RNA for an antigen-specific binding molecule from an antigen-specific T-cell hybrid.
- Adenovirus vector-infected cells can escape adenovirus antigen-specific cytotoxic T-lymphocyte killing in vivo.
- Induction of antigen-specific class I-restricted cytotoxic T cells by soluble proteins in vivo.
- Baculovirus Vectors Elicit Antigen-Specific Immune Responses in Mice