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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
An innate response to allogeneic nonself mediated by monocytes
Daniel Zecher1, Nico van Rooijen, David M Rothstein
1Departments of Surgery, Immunology, and Medicine, Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|November 20, 2009
Summary
Innate immunity distinguishes self from nonself. Monocytes, a type of white blood cell, can recognize and respond to foreign cells (allogeneic nonself) without T or NK cells, suggesting novel innate allorecognition pathways.
Area of Science:
- Immunology
- Innate Immunity
- Allorecognition
Background:
- Mammalian innate immunity distinguishes self from microbial nonself.
- Mechanisms for distinguishing self from allogeneic nonself within the same species are less understood.
Purpose of the Study:
- To investigate how the innate immune system distinguishes allogeneic nonself.
- To explore the role of monocytes in allogeneic responses.
Main Methods:
- Studied cutaneous hypersensitivity in lymphocyte-deficient RAG(-/-) mice transplanted with allogeneic or syngeneic spleen cells.
- Utilized cell depletions (NK cells, monocytes/macrophages, neutrophils) and adoptive transfer experiments.
- Examined responses based on MHC and non-MHC genetic differences.
Main Results:
- RAG(-/-) mice showed specific skin responses to allogeneic cells, involving monocyte/macrophage and neutrophil infiltration.
- The response required prior sensitization and demonstrated memory characteristics.
- Monocyte depletion reduced the response, while adoptive transfer of monocytes conferred alloimmunity.
- Monocyte-mediated alloimmunity was dependent on non-MHC genetic disparities.
Conclusions:
- Monocytes can mount a specific response to allogeneic nonself, a previously unrecognized function.
- Suggests the existence of innate allorecognition strategies in mammals distinct from NK cell-mediated mechanisms.
- Highlights the role of monocytes in recognizing and responding to genetically disparate cells.
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