Back to Search
Start Over
In vivotumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL-2
- Source :
- European Journal of Immunology. 40:813-823
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Missing-self-reactivity can be mimicked by blocking self-specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumor cells. Using a mouse model, we investigated whether Ab-mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumor cells, would still allow self-tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H-2(b)) NK cells were blocked with F(ab')(2) fragments of the mAb 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence-labeled syngeneic lymphoma line cells but not of syngeneic spleen cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK cell-dependent and specifically induced by Ly49C/I blockade. Moreover, selective tumor rejection was maintained after treatment with 5E6 F(ab')(2) for 9 wk, arguing against the induction of NK cell anergy or autoreactivity during this time. Combination therapy using 5E6 F(ab')(2) together with high dose IL-2 treatment further increased lymphoma cell rejection. In addition, combination therapy reduced growth of melanoma cell line tumors established by s.c. inoculation 3 days before start of treatment. Our results demonstrate that inhibitory receptor blockade does not result in attack on normal cells, despite potent reactivity against MHC class I-expressing tumors.
- Subjects :
- Lymphoma
medicine.medical_treatment
Immunology
Cell Separation
Immunoglobulin Fab Fragments
Mice
Interleukin 21
MHC class I
medicine
Animals
Immunology and Allergy
Lymphokine-activated killer cell
biology
Janus kinase 3
Lymphoblast
Antibodies, Monoclonal
Neoplasms, Experimental
Immunotherapy
Flow Cytometry
Killer Cells, Natural
Self Tolerance
Cytokine
biology.protein
Interleukin 12
Cancer research
Interleukin-2
NK Cell Lectin-Like Receptor Subfamily A
Subjects
Details
- ISSN :
- 15214141 and 00142980
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi.dedup.....efe74d466671d7e8a106f314fa83bd4c