Researchers Use Stem Cells to Produce CD8 Cells Targeting HIV

		SUMMARY: Researchers have found a way to engineer human stem cells to produce CD8 killer T-cells that specifically target and destroy HIV-infected cells, according to a study reported in the December 7, 2009 issue of the open access journal PLoS One. Many challenges remain, however, before this process could be widely used to treat HIV or other diseases caused by a malfunctioning immune system.

By Liz Highleyman

Scott Kitchen from the David Geffen School of Medicine at the University of California at Los Angeles (UCLA) and colleagues tested whether it would be possible to genetically program human stem cells to target HIV.

"The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at re-establishing immune control represents a potentially powerful approach towards treating persistent viral infections," the study authors wrote as background.

The investigators engineered hematopoietic stem cells to evolve into mature CD8 cytotoxic ("killer") T-cells that express a cloned "transgenic" human anti-HIV T-cell receptor, which enables the cells to recognize HIV. The engineered killer T-cells were grown in human thymus tissue implanted into specially bred mice lacking an immune system.

Hematopoietic stem cells in the bone marrow are precursors for all types of blood cells. (The controversial stem cells that feature in political headlines are a different sort, pluripotent stem cells, which have the potential to evolve into any type of cell in the body.)

In children, newly produced T-cells migrate to the thymus, an organ in the chest where they mature and learn to recognize pathogens; however, the thymus shrinks and its function declines with age.

The researchers determined that anti-HIV T-cell receptor transduced stem cells implanted into mice led to maturation of a large population of multi-functional HIV-specific CD8 cells that could recognize and kill infected cells that present viral antigens on their surface.

Thus, the investigators concluded, "through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T-cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control."

"In all, our data demonstrate that hematopoietic stem cells transduction with a human viral antigen-specific T-cell receptor can be utilized to generate antigen-specific CTL," they added in their discussion. "Our data strongly suggest that this strategy should be pursued as an effective therapy to combat viral infection in humans."

"We have demonstrated in this proof-of-principle study that this type of approach can be used to engineer the human immune system, particularly the T-cell response, to specifically target HIV-infected cells," Kitchen said in a UCLA news release. "These studies lay the foundation for further therapeutic development that involves restoring damaged or defective immune responses toward a variety of viruses that cause chronic disease, or even different types of tumors."

This basic research remains far from practical application, however, due to the difficulty and expense of cloning and producing CD8 cells from each specific individual to be treated.

Division of Hematology-Oncology, Division of Infectious Diseases, Department of Microbiology, Immunology & Molecular Genetics, and UCLA AIDS Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA; Departments of Pediatrics and Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY.

12/11/09

Reference
SG Kitchen, M Bennett, Z Gali?, and others. Engineering Antigen-Specific T Cells from Genetically Modified Human Hematopoietic Stem Cells in Immunodeficient Mice. PLoS One 4(12): e8208 (Free full text). December 7, 2009.

Other source
E Rivero. UCLA researchers demonstrate that stem cells can be engineered to kill HIV. University of California at Los Angeles. Press release. December 7, 2009.