A promising approach to immunotherapy involves the loading of dendritic cells (DCs) with genetic material to facilitate sustained expression of a relevant antigen in this population of potent antigen presenting cells (APCDendritic cells play a central role in controlling immunity. Antigen is initially processed by immature DCs, which subsequently undergo maturation involving phenotypic and functional changes that enable DC to mediate specific T and B cell activation in a highly effective manner. In tumor-bearing hosts, antitumor immunity can be compromised because tumor antigens fail to elicit immune mechanisms to resist tumor growth. This outcome is possibly related to a deficiency of DC expressing tumor antigens. Accordingly, strategies to vaccinate against tumor-specific antigens utilizing DC are being developed to bolster anti-tumor immunity.
The study suggests DSG arrests DC maturation. The unusual synergy of immunotoxin and DSG apparently involves coincidental reduction in lymph node T cell mass and mature DC, a transient circumstance favoring development of stable tolerance.
In this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12.
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