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Studies show Tim-3 proteins key to immune responses

not found on the surface of either [non-activated] resting T-cells or on activated T-cells other than TH1 helper cells, we hypothesized that Tim-3 served to limit and control ongoing TH1-dependent immune responses," explains Strom. "The particular pattern of Tim-3 expression that was found in these two studies suggests that it plays a key role in squelching activation of TH1 T-cells. Nature must have wanted us to have such a mechanism so that once you have created immunity, you have a timely means of 'turning off' the immune attack," he adds.

Strom and his colleagues looked at autoimmune diabetes in mice, a condition known to be caused by a TH1 response against insulin-producing cells. In a mouse model of tissue transplants, they found that mice with no Tim-3 rapidly rejected the transplants, despite receiving treatments that normally ensured transplant survival. Likewise, in their paper, Kuchroo and colleagues demonstrated that Tim-3 deficiency prevented mice from acquiring a state of "immune tolerance," which can normally be attained by administering high doses of protein.

"This clearly shows that one of the primary functions of the Tim-3 molecule is not only to regulate the expansion of TH1 cells, but also to regulate induction of tolerance in these cells," explains Kuchroo. "The method to block the Tim-3/Tim-3L interaction with the soluble Tim-3Ig, though not useful for autoimmunity, may prove very useful in enhancing anti-tumor immunity and anti-microbial immunity." Strom adds that the new findings suggest two important ways in which the Tim-3 pathway could be harnessed: First, by enhancing the Tim-3 signal, the response of TH1 cells could be diminished, thereby creating immune tolerance, and squelching the development of autoimmune diseases or preventing organ rejection.

And second, by blocking the Tim-3 pathway, TH1 responses could be amplified, thereby helping the immune system mount a more vigorous attack against foreign microbes or tumor
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
30-Oct-2003


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