| RRC ID |
43279
|
| 著者 |
Baba T, Iwasaki S, Maruoka T, Suzuki A, Tomaru U, Ikeda H, Yoshiki T, Kasahara M, Ishizu A.
|
| タイトル |
Rat CD4+CD8+ macrophages kill tumor cells through an NKG2D- and granzyme/perforin-dependent mechanism.
|
| ジャーナル |
J Immunol
|
| Abstract |
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.
|
| 巻・号 |
180(5)
|
| ページ |
2999-3006
|
| 公開日 |
2008-3-1
|
| DOI |
10.4049/jimmunol.180.5.2999
|
| PII |
180/5/2999
|
| PMID |
18292522
|
| MeSH |
Animals
CD4 Antigens / biosynthesis*
CD8 Antigens / biosynthesis*
COS Cells
Cell Communication / genetics
Cell Communication / immunology
Cell Line, Tumor
Chlorocebus aethiops
Cytotoxicity, Immunologic* / genetics
Granzymes / biosynthesis
Granzymes / genetics
Granzymes / physiology*
Growth Inhibitors / biosynthesis
Growth Inhibitors / genetics
Growth Inhibitors / physiology
Humans
Killer Cells, Natural / immunology
Killer Cells, Natural / metabolism
Lectins, C-Type / physiology*
Ligands
Macrophages / immunology*
Macrophages / metabolism
Mice
NK Cell Lectin-Like Receptor Subfamily K
Perforin / antagonists & inhibitors
Perforin / physiology*
Rats
Rats, Inbred F344
Rats, Wistar
Receptors, Immunologic / physiology*
Receptors, Natural Killer Cell
|
| IF |
4.886
|
| 引用数 |
18
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RCN-9(RCB0511)
P-815(RCB1167) |
