The principal mechanism of acute cellular rejection is CTL-mediated killing of cells in the graft (Fig. 16-8B). On histologic examination, this type of rejection is characterized by infiltrates of lymphocytes, which invade and destroy graft components (Fig. 16-9B). There are many lines of evidence that support the role of CTLs in acute cellular rejection. The cellular infiltrates present in grafts undergoing this type of rejection are markedly enriched for CD8+ CTLs specific for graft alloantigens. In fact, the presence of mRNAs encoding CTL-specific genes (e.g., perforin and granzyme B) is sometimes used as a specific and sensitive indicator of clinical acute rejection. Experimentally, alloreactive CD8+ CTLs can be used to adoptively transfer acute cellular graft rejection. The destruction of allogeneic cells in a graft is highly specific, a hallmark of CTL killing. The best evidence for this specificity has come from mouse skin graft experiments using chimeric grafts that contain two distinct cell populations, one syngeneic to the host and one allogeneic to the host. When these skin grafts are transplanted, the allogeneic cells are killed without injury to the "bystander" syngeneic cells.
In addition to direct killing of the graft cells by CTLs, activated CD4+ helper T cells and CTLs produce cytokines that recruit and activate inflammatory cells, which also injure the graft.
In vascularized grafts such as kidney grafts, endothe-lial cells are major targets of acute rejection. Microvascu-lar endothelialitis is a frequent early finding in grafts undergoing acute rejection episodes. Endothelialitis or intimal arteritis in medium-sized arteries also occurs at an early stage of acute rejection and is indicative of severe rejection, which, if left untreated, will likely result in acute graft failure. Both CD8+ and CD4+ T cells may contribute to endothelial injury.
Was this article helpful?
All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.