Measuring the quantity of a certain type of immune cell DNA in the blood could help physicians predict whether a bone marrow stem cell transplant will successfully restore a population of infection-fighting cells called T lymphocytes in a child. This research, by investigators at St. Jude Children's Research Hospital, is published in the journal Blood.
This finding could help physicians predict whether children receiving such a transplant will experience either failure or significant delay in the reconstitution of the T cell population. Moreover, if the transplant is successful, T cells arising from donated stem cells will be available to launch attacks on the patient's cancer cells--the so-called "graft-versus-tumor" response. This will further improve the patient's outcome following initial therapy (chemotherapy, irradiation and surgery).
Physicians sometimes treat patients with stem cell transplants as part of therapy for a variety of diseases such as leukemia or sickle cell disease. In these cases physicians eliminate the patients' own stem cells that produce cancerous white cells or faulty red cells and replace them with healthy stem cells from donors. If the transplants succeed, the donated stem cells repopulate the blood with healthy red and white cells.
The St. Jude team showed that the more copies of tiny rings of DNA called signal-joint TRECs (sjTRECs) there are in a child's blood, the more likely it is that the patient's thymus gland can act as an efficient factory where stem cells become T cells. The thymus is an immune system organ behind the breastbone that processes immature "precursor" immune cells into specialized T cells.
T lymphocytes are specialized immune cells carrying proteins called receptors on their surface. The target that a T cell recognizes and attacks depends on the makeup of its receptor, which is constructed of protein building blocks. Each protein building block is coded by a specific gene. sjTRECs form during a "mix-and-match" rearrangement of these genes into any one of countless combinations. The rings represent sections of DNA cut out of chromosomes during the mixing and matching of genes that are chosen to build a particular receptor. Each T cell uses the resulting combination of genes to make a receptor that lets the cell recognize a specific target. When stimulated to multiply, each of those cells produce an army of immune cells against their designated target.
Specific infectious organisms or other foreign substances stimulate T cells to divide and multiply in order to form an attacking army. However, the sjTRECs don't multiply when the original T cells divide and multiply. Instead, the more T cells that are produced in the blood as the parent cells containing sjTRECs divide and produce daughter cells, the more the sjTRECs in those original T cells get "diluted" within the growing army of these immune cells. This proves that high levels of sjTREC in blood means that a large number of stem cells have been converted to parent T cells--each of which targets a specific foreign substance, according to Rupert Handgretinger, M.D., Ph.D., director of Stem Cell Transplantation at St. Jude and co-director of the Transplantation and Gene Therapy Program.