Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

被引：20

作者：

Jimenez-Perez, Miriam I. ^{[1
,2
]}

Jave-Suarez, Luis F. ^{[2
]}

Ortiz-Lazareno, Pablo C. ^{[2
]}

Bravo-Cuellar, Alejandro ^{[2
,3
]}

Gonzalez-Ramella, Oscar ^{[1
]}

Aguilar-Lemarroy, Adriana ^{[2
]}

Hernandez-Flores, Georgina ^{[2
]}

Pereira-Suarez, Ana L. ^{[1
]}

Daneri-Navarro, Adrian ^{[1
]}

del Toro-Arreola, Susana ^{[1
]}

机构：

[1] Univ Guadalajara, Ctr Univ Ciencias Salud, Dept Fisiol, Immunol Lab, Guadalajara 44430, Jalisco, Mexico

[2] Ctr Investigac Biomed Occidente, Inst Mexicano Seguro Social, Div Immunol, Guadalajara, Jalisco, Mexico

[3] Univ Guadalajara, Ctr Univ Altos, Dept Ciencias Salud, Guadalajara 44430, Jalisco, Mexico

来源：

BMC IMMUNOLOGY | 2012年 / 13卷

关键词：

NK cells; NKG2D; MICA; MICB; ULBP; Cervical cancer; I-RELATED CHAIN; CYTOMEGALOVIRUS GLYCOPROTEIN UL16; CLINICAL-SIGNIFICANCE; CYTOKINE SECRETION; ADAPTIVE IMMUNITY; LIGANDS; PROTEIN; CYTOTOXICITY; INNATE; MOLECULES;

D O I：

10.1186/1471-2172-13-7

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. Results: We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. Conclusions: Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.

引用

页数：10

共 51 条

[21] Human Placenta Expresses and Secretes NKG2D Ligands via Exosomes that Down-Modulate the Cognate Receptor Expression: Evidence for Immunosuppressive Function [J].