- Paper Report
- Open Access
Regulatory function of anergized T cells
- Steven C Ghivizzani1
© Biomed Central Ltd 2001
- Received: 27 July 2001
- Accepted: 24 September 2001
- Published: 24 September 2001
- gene transfer
Through cross-presentation, antigen-presenting cells (APC) acquire tissue antigens and then either prime or tolerize mature T cells. The pathway toward either direction is not completely understood, but is thought to involve alternate interactions - of MHC antigens, T-cell receptors and costimulatory molecules - between the two cell types. It has been postulated that anergized T cells arising from this process may not be inert, but instead, actively regulate immune responses; however, this has not been demonstrated in vivo. To study the immunomodulatory capacity of these cells, the authors make use of a novel system whereby anergic T cells of known antigen specificity are generated in transgenic mice; immune response following local expression of antigen delivered by adenovirus or adeno-associated virus (AAV) vectors are then evaluated.
Transgenic mice were generated containing the gene for influenza hemaeglutinin (HA) under control of the Ig? light chain promoter and enhancer. This enabled expression of HA on circulating hematopoietic cells. These mice were found to be tolerant of HA expression in muscle following AAV mediated gene transfer. In the same mice, adenoviral mediated expression of HA in muscle was quickly terminated due to a local immune response as evidenced by local muscle fiber destruction. This was attributed to coexpression of vector-encoded native adenoviral proteins. In transgenic mice that expressed a T-cell receptor specific for HA (TCR-HA), HA expressing muscle cells were quickly eliminated by the immune system following delivery with either vector. Anergic T cells were generated in double transgenic mice that express HA as well as TCR-HA. In these mice, regardless of viral vector used for delivery to muscle, HA expression was found to be stable, Following adoptive transfer into nude mice, anergic T cells were capable of blocking immune responses of T cells from TCR-HA mice to either HA or viral antigens of a recombinant adenoviral vector.
Recombinant viral vectors, immunohistochemistry, cytotoxic T lymphocyte assay, adoptive transfer, transgenic mice