Heart Grafts Avoid Rejection

Main Category: Transplants / Organ Donations
Article Date: 07 Apr 2007 - 20:00 PDT


Rats treated with a drug known as CD40Ig have been shown to accept heart grafts from rats that are not genetically identical. Although it is known that CD40Ig disrupts the interaction between CD40 and CD40L on different immune cells, exactly how this prevents heart graft rejection in rats had not been determined.

In a study that appears in the April issue of the Journal of Clinical Investigation, Ignacio Anegon and colleagues from Centre Hopitalier Universitaire de Nantes, France, identified in rats treated with CD40Ig a population of regulatory immune cells that express CD8 and low levels of CD45RC. These cells were essential for the heart graft to survive and when transferred to normal mice they prevented the rejection of a subsequent heart graft in the absence of CD40Ig treatment. In vitro, these cells produced a soluble factor known as IFN-gamma that induced endothelial cells in the heart graft to express a protein known as IDO. Importantly, neutralizing either IFN-gamma or IDO in vivo caused heart graft rejection in rats treated with CD40Ig. This study therefore describes a mechanism by which treatment with CD40Ig can result in the prevention of heart graft rejection.

As discussed in an accompanying commentary, the importance of IFN-gamma for preventing the rejection of heart grafts is likely to surprise many as it has long been considered a soluble factor that enhances inflammation. However, as Jingwu Zhang from the Institute of Health Sciences in China notes, "the paradoxical actions of IFN-gamma appear to follow the principle of yin and yang, as do many of nature's paradoxes. That is, the roles of IFN-gamma only exist in a well-defined, integrated system in which the two elements of a proinflammatory process (yang) and an antiinflammatory/regulatory process (yin) interact to achieve and maintain balance."

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TITLE: CD40Ig treatment results in allograft acceptance mediated by CD8+CD45RClow T cells, IFN-gamma, and indoleamine 2,3-dioxygenase

AUTHOR CONTACT:
Ignacio Anegon
Centre Hopitalier Universitaire de Nantes, Nantes, France. http://www.univ-nantes.fr.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28801

ACCOMPANYING COMMENTARY
TITLE: Yin and yang interplay of IFN-gamma in inflammation and autoimmune disease

AUTHOR CONTACT:
Jingwu Zhang,
Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Shanghai, China.

View the PDF of this article at: https://www.the-jci.org/article.php?id=31860

Contact: Karen Honey
Journal of Clinical Investigation

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