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An innate response to allogeneic nonself mediated by monocytes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zecher, Daniel Rothstein, David M. Lakkis, Fadi G. Shlomchik, Warren D. Van Rooijen, Nico
Description	Country affiliation: United States Author Affiliation: Zecher D ( Departments of Surgery, Immunology, and Medicine, Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.)
Abstract	The mammalian innate immune system has evolved diverse strategies to distinguish self from microbial nonself. How the innate immune system distinguishes self-tissues from those of other members of the same species (allogeneic nonself) is less clear. To address this question, we studied the cutaneous hypersensitivity response of lymphocyte-deficient RAG(-/-) mice to spleen cells transplanted from either allogeneic or syngeneic RAG(-/-) donors. We found that RAG(-/-) mice mount a specific response to allogeneic cells characterized by swelling and infiltration of the skin with host monocytes/macrophages and neutrophils. The response required prior priming with allogeneic splenocytes or skin grafts and exhibited features of memory as it could be elicited at least 4 wk after immunization. Neither depletion of host NK cells nor rechallenging immunized mice with F(1) hybrid splenocytes inhibited the response, indicating that the response is not mediated by NK cells. Depletion of host monocytes/macrophages or neutrophils at the time of rechallenge significantly diminished the response and, importantly, the adoptive transfer of monocytes from alloimmunized RAG(-/-) mice conferred alloimmunity to naive RAG(-/-) hosts. Unlike NK- and T cell-dependent alloresponses, monocyte-mediated alloimmunity could be elicited only when donor and responder mice differed at non-MHC loci. These observations indicate that monocytes mount a response to allogeneic nonself, a function not previously attributed to them, and suggest the existence of mammalian innate allorecognition strategies distinct from detection of missing self-MHC molecules by NK cells.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Immunity, Innate Isoantigens Immunology Monocytes Animals B-lymphocytes H-2 Antigens Genetics Homeodomain Proteins Immunologic Memory Killer Cells, Natural Mice Mice, Inbred Balb C Mice, Inbred C3h Mice, Inbred C57bl Mice, Knockout Metabolism Species Specificity Spleen Cytology Transplantation T-lymphocytes Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Donor deficiency of decay-accelerating factor accelerates murine T cell-mediated cardiac allograft rejection.

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Cutting edge: innate memory CD8+ T cells are distinct from homeostatic expanded CD8+ T cells and rapidly respond to primary antigenic stimuli.

An innate response to allogeneic nonself mediated by monocytes.

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An innate response to allogeneic nonself mediated by monocytes.