Interleukin Treatment Activates Tolerant T Cells

Cancer researchers have found a way to "reactivate” tolerant CD8+ T cells so that they become able to attack and destroy tumor cells.

It has proven difficult to stimulate effective CD8+ T cell–mediated responses to tumors, as the T-cells develop tolerance to relevant tumor antigens, which are in most cases also expressed in normal tissues.

Investigators at the University of Washington (Seattle, USA) worked with a transgenic T-cell receptor (TCR) mouse model in which peripheral CD8+ T cells specific for a candidate tumor antigen that was also expressed on normal liver cells were tolerant, failing to proliferate or secrete interleukin (IL-2) in response to the antigen.

Senior author Dr. Philip Greenberg, professor of medicine and immunology at the University of Washington, explained, "Those CD8+ T cells that can recognize such tumor antigens but evade thymic deletion are potentially harmful, and thus are held in check inside the body by mechanisms that make them tolerant of the protein even if it is encountered on a tumor cell.”

The investigators isolated tolerant CD8+ T cells from the mice and treated them in vitro with interleukin-15 (IL-15). Results published in the February 12, 2006, online edition of Nature Medicine revealed that after treatment and return to the animals, the cells acted as efficient tumor killers. Despite potential autoimmune problems, the authors concluded that, "It is precisely these cells that might be most effective in tumor therapy, albeit with some potential toxicity.”


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