Modified T Cells Thwart Autoimmune Attack

Foxp3-expressing regulatory T cells mediate peripheral immune tolerance and suppress undesirable immune responses. Gene transfer techniques may be used to instill the ectopic expression of Foxp3 into conventional T cells. These cells then become available for therapeutic use in the prevention of autoimmunity and transplant rejection.

In a paper published in the November 11, 2008, online edition of the journal PLoS Biology the investigators described a genetic method for implanting a drug-inducible form of Foxp3 (iFoxp3) into normal T cells in an animal model of rheumatoid arthritis. They found that iFoxp3-transduced cells homed "correctly” into secondary lymphoid organs, where they expanded and participated in immune responses. Upon drug-based induction of iFoxp3, the cells assumed a regulatory T cell phenotype and started to suppress the response they initially partook in without causing systemic immunosuppression. This approach was then used to suppress collagen-induced arthritis, in which conventional Foxp3-transduced cells failed to show any effect.

Senior author Dr. Alexander Betz, research group leader at the MRC Laboratory of Molecular Biology, explained, "We have generated a modified form of Foxp3 which can be introduced into immune cells using genetic engineering techniques and then activated by a simple injection. When administered to and activated in animal models of arthritis, the modified cells inhibit or even reverse the disease process.”

"We will develop a human Foxp3 factor and then assess its function in human arthritis models,” said Dr Betz. "To be viable as a therapeutic option, the regulatory cells must fulfill certain criteria; they must be tissue matched to the patient for compatibility; they must only block the targeted disease and not the whole body immune response; and they have to home correctly to their target tissue. Establishing these criteria will be the key focus of our research. If Foxp3 functions as a key developmental switch in human immune cells, there is potential for a new avenue of therapy development that could transform arthritis treatment.”

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MRC Laboratory of Molecular Biology