While many types of T lymphocytes exist, differentiated by their molecular makeup and the roles they play, CD4 and CD8 cells are considered the "normal population" responding to threatening antigens. But in these studies, most T cells present within the tumors were "double-negative," expressing neither CD4 nor CD8, but instead exhibiting abnormal characteristics.

"While most studies assign T cell defectiveness and death to the tumor environment, we now know more about the kinds of T cells that are susceptible and how they become defective. This allowed us to target novel properties to prevent or reverse the defects," said Christopher J. Wheeler, PhD, research scientist and the paper's senior author. "The T cell defects could be incurred independent of their reactivity to the tumor per se, and on a general level involved signals for survival."

T cells normally receive "survival" signals provided by signaling molecules or certain hormones. In the absence of these survival signals, the cells simply die by default.

"These signals are usually available in the body but they evidently are not available to T cells in tumors," said Dr. Wheeler. "We conducted an experiment to test this observation, adding back the molecules that can induce such signals, and we found a reduction in the abnormal T cells."

The recent research also provides new insight into another aspect of the relationship between tumors and defective T cells. Because those T cells responding to a tumor are believed to be specifically reactive to that tumor antigen, it has been assumed perhaps incorrectly that the T cell defects were in some way related to antigen-specificity and reactivity.

"We placed non-activated and non-tumor-specific T cells into tumors and found that they readily became defective. This runs counter to the predominant paradigm holding that de
'"/>

Contact: Sandra Van
sandy@vancommunications.com
1-800-880-2397
Cedars-Sinai Medical Center
21-Jan-2004