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Suppressor T cells, rebranded as regulatory T cells, emerge from the wilderness bearing surface markers
  1. T T MacDonald
  1. Division of Infection, Inflammation, and Repair, Mailpoint 813, Level E, South Block, Southampton General Hospital, Southampton SO16 6YD, UK; t.t.macdonald@soton.ac.uk

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Regulatory T cells express the glucocorticoid-induced tumour necrosis factor receptor family related gene (GITR) and antibodies against this receptor block regulatory cell activity. Signaling through this receptor may be involved in diseases where normal immune tolerance is broken, such as inflammatory bowel disease or autoimmune gastritis.

The 1970s and early 1980s were the heyday of cellular immunology. Complicated circuits of T cells were constructed in which helper cells were inhibited by suppressor cells which in turn were inhibited by contrasuppressor cells, and so on. By and large the actual experiments involved mixing different populations of T cells and B cells together in vitro and measuring the antibody response to the major human pathogens, sheep erythrocytes, or haptenated synthetic polymers. If the response went down, suppressor cell activity was evident. Suppressor cells were considered to be a lineage of CD8+ T cells, so that CD8 cells were either cytotoxic cells or suppressor cells. In the early to mid 1980s however, suppressor T cell research fell dramatically out of fashion. As molecular immunology took over, cellular immunology was seen as unsophisticated black magic. CD4+ helper T cells were cloned, as were cytotoxic CD8 T cell clones, but no suppressor T cell clones were made. In fact cellular immunology became a term of abuse. For those of us who teach immunology to medical students the existence of suppressor T cells was an embarrassment, dealt with by the phrase “nobody believes in these cells anymore”.

CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)—a …

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