Regardless, our results imply that numerous mechanisms underlie antigen-specific CD8+ T tolerance in the leukemia-bearing host and suggest that by the point at which a patient is diagnosed with acute leukemia, high-affinity leukemia-specific CD8+ T cells may be largely absent, having already been deleted, leaving behind a pool of exhausted, lower-affinity CD8+ T cells, the function of which may or may not be restorable with immunotherapeutic intervention. The gene discussed is CD8A; the disease is acute leukemia.