Thursday, 31 January 2013

A subset of T cells provide new insight into the mechanism of Graft Versus Host Disease

The term leukemia covers a range of haematological malignancies (cancers of blood cell origin). Patients can be treated by radiation or multi-drug chemotherapy. Recent research has focused on single agent therapeutics for use alone, or in combination with established treatments. Even difficult to treat leukemias such as chronic lymphocytic leukemia (CLL) have seen advances

However, the treatment of haematological malignancies usually involves high doses of chemo- and radio-therapy, which kills cancerous blood cells but also affects the body's ability to repopulate the blood with healthy white blood cells. To combat this, cancer treatment can be followed up with a replacement of the bone marrow or blood stem cells by transplantation from a donor. One very unfortunate side effect of this transplantation is the response of the transplanted (graft) cells to the host cells, this is known as Graft Versus Host Disease (GVHD). To treat GVHD, patients are given drugs to suppress the graft cell immune response, however these drugs can have severe side effects.

A very interesting research article published in the journal PLoS One, by van der Waart et al from The Netherlands, addresses one mechanism by which GVHD develops in patients treated for haematological malignancies by stem cell transplantation.

A recently discovered subtype of white blood cells, T cells called Th17 cells which produce a small signalling protein called IL-17, have been implicated in GVHD. This present study assessed the white blood cell content of patients with a range of haematological malignancies treated in the manner described above. They found that a subpopulation of Th17 cells which had high levels of the protein CD161 on their surface were resistant to the  effects of immuno suppressive drug treatment. These cells are protected by expression of a transporter on their surface (ABCB1) that removes the drug which would normally prevent their growth.

An interesting observation was that in patients with GVHD the number of CD161 expressing cells in the blood was decreased. The study goes on to show that in fact these cell relocate from the blood to tissue sites where GVHD is visible. These cells are able to respond to a small signalling protein, a chemokine called CCL20, which is enriched in tissue from patients with GVHD and  potentially pulls these cells from the blood into the tissue. An elegant use of an imaging technique known as immuno fluorescence, showed that the cells found in GVHD tissue indeed contains cells which are T cells expressing high levels of CD161 on their surface as well, as the protein which recognises CCL20.

This study provides two observations that could be potentially beneficial for the management of GVHD: a decrease in the number of CD161 expressing white blood cells in the blood of patients following reconstitution by stem cell transplantation may act as a marker for patients likely to develop GVHD. Additionally, further understanding of the role of this subset of T cells in GVHD may give rise to novel treatments for the management of GVHD.

Mentioned Articles

van der Waart AB, van der Velden WJ, van Halteren AG, Leenders MJ, Feuth T, Blijlevens NM, van der Voort R, Dolstra H. (2012)
Decreased levels of circulating IL17-producing CD161+CCR6+ T cells are associated with graft-versus-host disease after allogeneic stem cell transplantation.
PLoS One. 2012;7(12):e50896. doi: 10.1371/journal.pone.0050896. Epub 2012 Dec 4. (2009) About graft versus host disease (GVHD) : Cancer Research UK : CancerHelp UK. [online] Available at: [Accessed: 31 Jan 2013].

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