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Hematopoietic cells and radioresistant host elements influence natural killer cell differentiation
M Sykes1, M W Harty, F M Karlhofer
1Transplantation Research Biology Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129.
The Journal of Experimental Medicine
|July 1, 1993
Summary
Major histocompatibility complex (MHC) molecules on bone marrow-derived cells and radioresistant host cells influence natural killer (NK) cell differentiation. MHC expression on hematopoietic cells downregulates Ly-49 expression on NK cells, independent of the thymus.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- T cell development involves selection processes mediated by host elements and bone marrow-derived cells.
- Factors governing natural killer (NK) cell repertoire development, particularly in relation to major histocompatibility complex (MHC) phenotypes, are less understood.
- Ly-49 expression on a subset of NK cells in H-2b mice is influenced by MHC interactions, notably with Dd.
Purpose of the Study:
- To analyze the influence of donor and host MHC on a specific NK cell subset using murine bone marrow transplantation models.
- To investigate how MHC expression on hematopoietic cells affects Ly-49 expression in NK cells.
- To determine the role of radioresistant host elements expressing MHC in NK cell differentiation.
Main Methods:
- Utilized murine bone marrow transplantation models, including mixed allogeneic chimeras and fully allogeneic chimeras.
- Administered T cell-depleted allogeneic and host-type marrow to lethally irradiated recipients.
- Examined Ly-49 expression on NK cells under varying MHC expression scenarios on donor and host cells.
Main Results:
- Expression of H-2a on bone marrow-derived cells was sufficient to downregulate Ly-49 expression on both H-2a and H-2b NK cells, independent of the thymus.
- H-2a expressed on radioresistant host elements also led to Ly-49 downregulation on donor B10 NK cells in fully allogeneic chimeras.
- Lower levels of H-2a on F1 hybrid cells induced more significant Ly-49 downregulation on NK cells when presented on donor marrow compared to radioresistant host cells.
Conclusions:
- NK cell differentiation is primarily determined by interactions with MHC molecules expressed on bone marrow-derived cells.
- MHC antigens expressed on radioresistant host elements play a secondary role in NK cell differentiation.
- These findings elucidate key mechanisms governing NK cell repertoire development in response to MHC interactions.