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Dendritic Cells: Rabble-Rousers after Stem Cell Transplantation

Apr 16, 2014 1:00:50 PM / by Daisy

Stem cell transplantation is often the only option for patients who have certain blood cancers. Unfortunately, this last resort can sometimes bring more harm than good. Graft versus host disease (GVHD), is a common complication that affects 50% of transplant patients. GVHD is not an issue if the patient's own stem cells are transplanted back. However, GVHD can become an issue, sometimes fatal, when stem cells from another donor are used.

dendritic cells Dendritic cells - players in GVHD. Image Credits: Wiki Commons

Stem cell transplantation is the infusion of a mixture of cells typically found in peripheral blood mononuclear cells (PBMCs). GVHD occurs if the transplanted cells decide that the patient's body is foreign. When this happens, the newly transplanted cells attack the patient's body causing disease.  The players in GVHD are parts of the PBMCs present during normal times such as dendritic cells and T cells.

Dendritic cells can be likened to a snitch who has alliances. They fly flags (MHC molecules) to communicate their alliance and they fly flags to show who all is present - such as by presenting proteins from invading bacteria and viruses (antigen presentation). T cells can be likened to soldiers. They interact with dendritic cells, find out if the enemy is present (bacteria and viruses), and go to war by mounting an immune response.

In the case of GVHD, dendritic cells act as rabble-rousers by flying too many flags that identify the patients’ body as foreign to initiate immune attacks. This attracts attention from T cells from the donor. The result of GVHD is when donor T cells mount an attack against the patient's body because they recognize the patient's organs as foreign.  Organs commonly affected by GVHD include the skin, gut, and liver.

Of course there is much interest in interfering with the cascade of events that lead to GVHD. Donor T cells have historically been the target of drugs for this disease. Recently though, the availability of new drugs has opened up the possibility of altering the effect that dendritic cells have in GVHD.

Proteasome inhibitors are a new class of drugs recently discussed for their use in GVHD. In a recent study, dendritic cells were isolated from PBMC and treated with a proteasome class of drugs. Then when these dendritic cells were introduced to T cells, the T cells were not excited [1]. In contrast, T cells were excited by dendritic cells that were not treated with proteasome inhibitors. This experiment has significance for the stem cell transplant patient. Proteasome inhibitor drugs can alter dendritic cells to disable them from becoming rabble-rousers in the patient. Under such conditions, the donor T cells would not become excited and would not attack the patient's body to cause GVHD.

Often times, as is the case here, drugs can be evaluated for more than one clinical condition. We at HemaCare are a reliable provider of human dendritic cells and other cells for research of drugs for unmet medical conditions.

Reference

[1] Al-Homsi AS, Lai Z, Roy TS, Kouttab N. Effect of novel proteasome and immunoproteasome inhibitors on dendritic cell maturation, function, and expression of IκB and NFκB. Transpl Immunol. 2013 Dec;29(1-4):1-6. PMID: 24103732.

 

Topics: GVHD, proteasome inhibitors, T Cells, Basic Research

Daisy

Written by Daisy

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