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NK cell tolerance in mixed allogeneic chimeras.
Yong Zhao1, Hideki Ohdan, Jennifer O Manilay
1Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 22, 2003
Summary
Natural killer (NK) cells in mixed allogeneic chimeras demonstrate specific tolerance to both donor and host antigens. This in vivo study reveals stable NK cell tolerance, unaffected by activating cytokines or receptor expression levels.
Area of Science:
- Immunology
- Transplantation Biology
- Cellular Immunology
Background:
- Altered inhibitory receptor expression on NK cells is observed in mixed allogeneic chimeras.
- Previous in vitro studies suggested a lack of mutual tolerance between donor and host NK cells.
- The in vivo tolerance status of NK cells in mixed chimeras remained largely unknown.
Purpose of the Study:
- To investigate in vivo whether NK cells in mixed allogeneic chimeras are tolerant to host and donor antigens.
- To determine if NK cell tolerance in chimeras can be broken by exogenous cytokines or altered receptor expression.
Main Methods:
- Utilized BALB/c-->B6 fully MHC-mismatched mixed chimeras.
- Assessed NK cell activation markers (B220, Thy-1.2) and bone marrow cell (BMC) rejection.
- Evaluated RMA lymphoma cell growth and Ly-49D receptor expression.
Main Results:
- NK cells in mixed chimeras showed no signs of activation and were specifically tolerant to donor and host BMCs.
- Chimeric mice rejected beta(2)-microglobulin-deficient BMCs but not BALB/c or B6 BMCs, unlike control B6 mice.
- Exogenous IL-2 did not break NK cell tolerance, and Ly-49D expression remained unchanged.
Conclusions:
- NK cells in mixed allogeneic chimeras exhibit stable, specific tolerance to both donor and host antigens in vivo.
- This tolerance is not dependent on activating cytokines or altered expression of the Ly-49D receptor.
- The underlying mechanisms responsible for maintaining NK cell tolerance in chimeras require further investigation.