A subset of antiviral immune cells could prevent CMV infections in bone marrow transplant recipients

A very small subset of antiviral immune cells, transplanted along with a donor's blood stem cells, could be enough to fight and even prevent the disease caused by cytomegalovirus (CMV) in patients receiving bone marrow transplants. This research, published in the Journal of Immunology (2015; doi:10.4049/jimmunol.1402757), was conducted in mice.

Bone marrow transplantation is a life-saving therapy for patients with blood cancers such as leukemia or lymphoma. However, the depletion of the patient's immune system prior to transplantation can put patients at risk for CMV infection, which can be life threatening in these immune-compromised patients.

Fifty percent to 80% of adults in the United States are infected with CMV, but the virus is kept under control by a healthy immune system. In patients with weakened immune systems, however, CMV can become reactivated and can cause life-threatening pneumonia, among other symptoms. Current treatment includes antiviral medication. But these drugs are not always well tolerated by patients, and they also harm the cells that bone marrow transplantation aims to replenish.

"We know that re-establishment of antiviral immunity in these patients is critical to fully control cytomegalovirus in bone marrow transplant recipients," said senior author Christopher Snyder, PhD, an Assistant Professor of Microbiology and Immunology at Thomas Jefferson University in Philadelphia, Pennsylvania.

"Our study suggests that, in addition to infusing stem cells that restore the bone marrow, life-long anti-CMV immunity may be rapidly restored by also infusing a subset of antiviral immune cells that have stem cell-like properties."

"The problem," said Snyder, "is that current methods for selecting antiviral immune cells may inadvertently limit the ability of those cells to restore life-long immunity."

To date, researchers have focused on developing anti-CMV immunotherapy around the fighter CD8 T effector cells that attack and kill virally infected host cells. These cells are selected and expanded in the laboratory to increase their numbers, but this process may limit their life-span and ability to divide.

Snyder and colleagues found that CMV-specific fighter T cells divided poorly in response to CMV infection or reactivation in mouse models.

Snyder's group showed that a small number of stem-cell like CD8 T cells, called memory cells, were enough to produce and repeatedly replenish all of the T-effector cells needed to fight the disease. The infused memory cells became major contributors to the recipient antiviral immune response, persisting for at least 3 months, and producing the fighter cells at a steady stream.

To survey whether these cells have counterparts in humans, the researchers compared the genomic fingerprint, which is the profile of genes that were turned up or down, of mouse and human memory T cells that were specific for CMV and found that the two had similar profiles. They concluded that human and mouse CMV-specific memory T cells are very similar populations. So, infusing similar cells could help control CMV infections and keep the disease from emerging in patients.

"Our data argue for developing new clinical trials focused specifically on using these T memory cells, in order to determine if it would indeed be better than current therapeutic options," said Snyder.

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