We are not talking about a rodent sandwich. This new type of laboratory mouse, a chimera called Bone Marrow Liver Thymic mice (BLT mice), created by researchers at UT Southwestern and University of Minnesota, should open new experimental possibilities to study human infections:
Normal mice are not susceptible to human-specific viruses, such as Epstein Barr virus and HIV, making it hard to study and craft drugs to target the viruses. Epstein Barr is a virus that causes mononucleosis.
So UT Southwestern researchers, working with University of Minnesota collaborators, generated human-mice “chimeras” – mice implanted with human tissues and human stem cells – that developed fully functional human immune systems and infection-fighting cells, such as T cells, throughout their bodies, according to a study published online today in Nature Medicine.
The T cells in the mice even mounted a potent immune response to toxic shock syndrome and infection by Epstein Barr.
In immune-deficient mice that are unable to reject human cells or tissues, researchers first implant the rodents with human tissues necessary to develop human T cells. Human blood stem cells, known as CD34+ cells, then are transplanted into the mice. CD34+ cells, which give rise to human T cells, B cells and other types of human cells that protect the body against foreign organisms and pathogens, are typically used to treat human cancer and blood and heart disorders.
In this latest study, UT Southwestern researchers and their Minnesota colleagues used this combination approach – human tissues and stem cells – to try to generate a new type of chimera that can develop T cells the same way as humans.
The resulting mice, known as Bone Marrow Liver Thymic mice (BLT mice), developed a human immune system with dramatically high human T cell and other cell counts in virtually all of their tissues, including the gut and lungs, sites of important immune response to diseases.
“The fact that virtually all human immune cells are adequately distributed in all the different mouse tissues has resulted in what is probably the most human-like immune system ever developed in mice,” Dr. Garcia said.