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Xenogeneic β2-Microglobulin Substitution Alters NK Cell Function
- Source :
- The Journal of Immunology. 179:1466-1474
- Publication Year :
- 2007
- Publisher :
- The American Association of Immunologists, 2007.
-
Abstract
- Recently, it has been shown that human beta(2)-microglobulin (h-beta(2)m) blocks the association between the NK cell inhibitory receptor Ly49C and H-2K(b). Given this finding, we therefore sought to assess the immunobiology of NK cells derived from C57BL/6 (H-2(b)) mice expressing exclusively h-beta(2)m. Initial analysis revealed that the Ly49C expression profile of NK cells from h-beta(2)m(+) mice was modified, despite the fact that H-2K(b) expression was normal in these mice. Moreover, the NK cells were not anergic in that IL-2 treatment of h-beta(2)m(+) NK cells in vitro enabled efficient lysis of prototypic tumor cell lines as well as of syngeneic h-beta(2)m(+) lymphoblasts. This loss of self-tolerance appeared to correlate with the activation status of h-beta(2)m(+) NK cells because quiescent h-beta(2)m(+) transplant recipients maintained h-beta(2)m(+) grafts but polyinosine:polycytidylic acid-treated recipients acutely rejected h-beta(2)m(+) grafts. NK cell reactivity toward h-beta(2)m(+) targets was attributed to defective Ly49C interactions with h-beta(2)m:H-2K(b) molecules. With regard to NK cell regulatory mechanisms, we observed that h-beta(2)m:H-2K(b) complexes in the cis-configuration were inefficient at regulating Ly49C and, furthermore, that receptor-mediated uptake of h-beta(2)m:H-2K(b) by Ly49C was impaired compared with uptake of mouse beta(2)m:H-2K(b). Thus, we conclude that transgenic expression of h-beta(2)m alters self-MHC class I in such a way that it modulates the NK cell phenotype and interferes with regulatory mechanisms, which in turn causes in vitro-expanded and polyinosine:polycytidylic acid-activated NK cells to be partially self-reactive similar to what is seen with NK cells derived from MHC class I-deficient mice.
- Subjects :
- Cytotoxicity, Immunologic
Graft Rejection
Immunology
Cell
Mice, Transgenic
Biology
Immunophenotyping
Mice
Interleukin 21
Cell Line, Tumor
MHC class I
medicine
Animals
Humans
Immunology and Allergy
Killer Cells, Lymphokine-Activated
Receptor
Mice, Knockout
Lymphokine-activated killer cell
Janus kinase 3
Lymphoblast
H-2 Antigens
Cell biology
Killer Cells, Natural
Mice, Inbred C57BL
Self Tolerance
medicine.anatomical_structure
Interleukin 12
biology.protein
Female
beta 2-Microglobulin
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 179
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....55cfd72d46cdefbf21ad3173b29ddcfc