Modified T Cells Thwart Autoimmune Attack

A method developed by immune-system researchers transforms T cells participating in autoimmune attacks on the body into regulatory cells that then thwart further autoimmune behavior.

Investigators at the MRC Laboratory of Molecular Biology (Cambridge, UK) focused their studies on a subset of T cells that express the protein Forkhead box p3 (Foxp3). 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