Experimental Support for the Ecoimmunity Theory: Distinct Phenotypes of Nonlymphocytic Cells in SCID and Wild-Type Mice

Cell Transplantation

Article

Uri Nevo¹  Jared Brazg²  David E. Ochayon²  Noa Kalay²  Boris M. Baranovski²  Justin Levinson²  Eli C. Lewis²  Peter Malkin²  Ronen Schuster²  Rotem Ben-Hamo³  Sol Efroni³  Ido Sloma³ 

[1] Department of Biomedical Engineering, The Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel;Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel;Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel;

关键词: Major histocompatibility complex (MHC) class I;    Lymphocytes;    Pancreatic islets;    Autoimmunity;    Ecoimmunity;   

DOI  :  10.3727/096368916X690809

 received in 2014-07-18, accepted in 2016-05-20,  发布年份 2016

来源: Sage Journals

【 摘 要 】

Immune tolerance toward “self” is critical in multiple immune disorders. While there are several mechanisms to describe the involvement of immune cells in the process, the role of peripheral tissue cells in that context is not yet clear. The theory of ecoimmunity postulates that interactions between immune and tissue cells represent a predator–prey relationship. A lifelong interaction, shaped mainly during early ontogeny, leads to selection of nonimmune cell phenotypes. Normally, therefore, nonimmune cells that evolve alongside an intact immune system would be phenotypically capable of evading immune responses, and cells whose phenotype falls short of satisfying this steady state would expire under hostile immune responses. This view was supported until recently by experimental evidence showing an inferior endurance of severe combined immunodeficiency (SCID)-derived pancreatic islets when engrafted into syngeneic immune-intact wild-type (WT) mice, relative to islets from WT. Here we extend the experimental exploration of ecoimmunity by searching for the presence of the phenotypic changes suggested by the theory. Immune-related phenotypes of islets, spleen, and bone marrow immune cells were determined, as well as SCID and WT nonlymphocytic cells. Islet submass grafting was performed to depict syngeneic graft functionality. Islet cultures were examined under both resting and inflamed conditions for expression of CD40 and major histocompatibility complex (MHC) class I/II and release of interleukin-1α (IL-1α), IL-1β, IL-6, tumor necrosis factor-α (TNF-α), IL-10, and insulin. Results depict multiple pathways that appear to be related to the sculpting of nonimmune cells by immune cells; 59 SCID islet genes displayed relative expression changes compared with WT islets. SCID cells expressed lower tolerability to inflammation and higher levels of immune-related molecules, including MHC class I. Accordingly, islets exhibited a marked increase in insulin release upon immunocyte depletion, in effect resuming endocrine function that was otherwise suppressed by resident immunocytes. This work provides further support of the ecoimmunity theory and encourages subsequent studies to identify its role in the emergence and treatment of autoimmune pathologies, transplant rejection, and cancer.

【 授权许可】

Unknown   
© 2016 Cognizant, LLC.

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