Days Post Challenge

Figure 5.13. Anti-CD137 restores LLC immunity in B cell reconstituted mice containing ||MT mice. Six C57BL/6 |MT mice were reconstituted with B cells from naïve BL/6 mice. Three mice were injected with 200 |g of anti-CD137 mAbs I.P. on days 0, 3 and 5 (filled diamonds) and the remaining three received Rat IgG. The mice were vaccinated with irradiated LLC cells on day 0 and challenged with viable LLC cells on day 14, and tumor progression was followed periodically thereafter.

whereas CD4+ CD25+ T cells or CD8+ T cells cannot. In addition, we find that suppression of anti-tumor immunity to LLC in B cell reconstituted, LLC vaccinated |MT mice can be overridden by injecting them with anti-CD137 (4-1BB) mAbs (Figure 5.13). At present it is not clear just how B cells or DC suppress the development of anti-tumor immunity or how anti-CD137 mAb treatment overrides B cell-mediated suppression in |MT mice. One hypothesis that we favor is that tumor antigen-experienced APC fail to mature and cannot adequately prime tumor-specific T cells. Perhaps this is due to their failure to adequately up-regulate their cell surface expression of costimulatory ligands such as CD40, CD80/86, 4-1BB-L, or other costimulatory or adhesion ligands. Regardless, failure to prime T cells to tumor antigens renders them anergic and this may be due to a direct effect of DC on rendering the T cell anergic, or inducing it to develop regulatory properties.

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