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Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Nonvascularized xenograft rejection is T cell mediated, but is
dependent on initial macrophage (M
) infiltration. We developed an
i.p. transplant model to define the roles of M and T cells in
xenograft rejection. Nonobese diabetic or BALB/c mice were injected
i.p. with xenogeneic, allogeneic, or syngeneic cells, and the
responding cells in subsequent lavages were assessed by flow cytometry
and adoptive transfer. Neutrophils and monocytes/elicited M were
rapidly recruited in response to xenogeneic pig (PK15 or spleen) cells
and, to a significantly lesser extent, allogeneic cells. These innate
responses preceded T cell infiltration and occurred in their absence in
SCID mice. Syngeneic cells induced negligible neutrophil or M
responses. Neutrophils and M induced by xenogeneic cells in SCID
mice stimulated T cell recruitment after transfer to immunocompetent
mice. T cells in turn were required for M activation and xenogeneic
cell rejection. Thus, M harvested from immunocompetent but not SCID
mice injected with xenogeneic cells expressed activation markers and
rejected xenogeneic cells when transferred into SCID mice. These
findings demonstrate the interdependent roles of M and T cells in
xenograft rejection. The requirement for M reflects their ability to
mount a rapid, local innate response that stimulates T cell recruitment
and, having received T cell help, to act as direct effectors of
rejection.
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