Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.79 (granzyme B)
 3,301 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously identified a subpopulation of monocyte/macrophage lineage cells expressing both CD4 and CD8. This subpopulation was expanded in rat peripheral blood and spleen after immunization with adjuvants containing killed tuberculosis germs. CD4+CD8+ monocytes/macrophages obtained from preimmunized rats exhibited a Th1-type cytokine/chemokine profile, expressed high levels of Fas ligand, perforin, granzyme B, and NKR-P2 (rat ortholog of human NKG2D), and killed certain tumor cells. In the present study, we confirmed that CD4+CD8+ monocytes/macrophages are distinct from splenic dendritic cells (DCs) or IFN-producing killer DCs. In vitro cytotoxic assays revealed that CD4+CD8+ macrophages killed tumor cells in a cell-cell contact-dependent manner and that expression of the retinoic acid early transcript 1 (a ligand for NKG2D) made tumor cells susceptible to killing by CD4+CD8+ macrophages. Furthermore, inhibitors of granzyme and perforin significantly decreased cytotoxic activities of CD4+CD8+ macrophages. Consistent with these in vitro findings, preimmunization with adjuvants containing killed tuberculosis germs elevated the expression of granzyme B in tumor-infiltrating CD4+CD8+ macrophages and significantly inhibited the growth of inoculated tumor cells. Our current work demonstrates that CD4+CD8+ macrophages are a unique subpopulation of monocyte/macrophage lineage cells that kill tumor cells in an NKG2D- and granzyme/perforin-dependent mechanism.
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PMID:Rat CD4+CD8+ macrophages kill tumor cells through an NKG2D- and granzyme/perforin-dependent mechanism. 1829 22