International Immunology, Vol 10, 1943-1955, Copyright © 1998 by Oxford University Press
JO Manilay, GL Waneck and M Sykes
Ly-49 molecules are used by NK cells to distinguish 'self' from 'non-
self', but the determinants of Ly-49 expression that allow this distinction
to be made are not understood. The education of NK cells for self/non-self
recognition was studied in murine mixed allogeneic bone marrow chimeras, in
which NK cells are of both host and donor origin. Marked alterations in
Ly-49 receptor expression were observed on both host and donor NK cells
developing in BALB/c --> B6 mixed chimeras. Ly-49A and Ly-49G2
expression was lower on host B6 NK cells of mixed chimeras compared to
non-transplanted B6 controls. Among donor BALB/c NK cells, Ly-49C
expression levels were reduced, but the proportion of Ly-49C+ cells was
increased, whereas Ly-49G2 expression was up-regulated compared to
non-transplanted BALB/c controls. Thus, Ly- 49 expression on donor and host
NK cells developing post-bone marrow transplantation evolves toward the
expression pattern of the host and donor strains respectively, due to the
presence of the allogeneic MHC. In vitro functional NK cell assays showed
that donor NK cells in mixed chimeras were not tolerant to host antigens
and that host NK cells were not tolerant to the donor. Our data are
consistent with a model in which MHC expression in the environment has a
dominant down-regulating effect on the expression of Ly-49 molecules that
recognize those MHC molecules, regardless of whether they are self or
allogeneic. This down- regulation, combined with the limited repertoire of
Ly-49 molecules, may not be sufficient to allow NK cells to be tolerant of
MHC antigens of a fully MHC-mismatched allogenic strain.
ARTICLES
Altered expression of Ly-49 receptors on NK cells developing in mixed allogeneic bone marrow chimeras
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
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