Tim-3 (T cell immunoglobulin domain, mucin domain) proteins are found on the surface of TH1-helper type T cells, which when activated become the body’s first line of defense against foreign microbes. “Activated TH1-type helper T cells both participate in and help orchestrate the attack on cells bearing proteins, thereby guarding against infection,” explains Terry Strom, chief of immunology at Beth Israel Deaconess Medical Center (BIDMC) and professor of medicine at Harvard Medical School. “Nature gave us these cells as a critical defense against microbes.” However, he adds, these same T-cell responses must always be carefully balanced — left unchecked, they can become overly aggressive, leading to inflammatory tissue injury and resultant autoimmune diseases. Two papers in Nature Immunology, by senior authors Strom and Brigham and Women’s Hospital immunologist Vijay Kuchroo found, for the first time, that Tim-3 proteins selectively serve as “checkpoints” for the immune system, helping to keep activated TH1 T-cell responses under control. Kuchroo is associate professor of neurology at Harvard Medical School. The Strom study was funded by the Juvenile Diabetes Research Foundation, the National Institute of Allergy and Infectious Diseases and the Center for Islet Transplantation at Harvard Medical School; the Kuchroo study was funded by the National Multiple Sclerosis Society and the National Institutes of Health.