Roland Martin and colleagues of the National Institute of Neurological Disorders and Stroke in Bethesda, MD, found that contact with an antigen-free dendritic cell provokes dramatic changes in human memory T cells—though not as profound as activation by an antigen. Gene expression shifts, boosting production of cytokines such as interferon gamma, and some T cells begin to divide slowly. Most importantly, the meeting lengthens the life of memory cells, more than doubling the percentage that survive five days in culture.
Working with naive mouse T cells, a team led by Alain Trautmann of the InstitutCochin de Génétique Moleculaire in Paris, France, saw similar results: greater survival and low-level proliferation in the T cells. “In the normal life of a lymphocyte, it will interact repeatedly with dendritic cells,” Trautmann says. “These repeated meetings are essential for survival.” To their surprise, the authors also detected a structure known as an immunological synapse at the junction between the cells. The synapse normally forms when a dendritic cell stimulates a T cell, but its formation was thought to require antigen.
Both groups agree that cellular contact may boost the immune system's readiness in two ways. By stimulating survival and slow reproduction, the interaction may help maintain stocks of T cells. And the low level of stimulation provided by dendritic cells seems to prime lymphocytes for action. However, Martin believes that the work also exposes a possible downside. He thinks that the surge in cytokine production may increase the risk of autoimmune diseases like multiple sclerosis in susceptible individuals. “The interaction may set up a certain environment that is conducive to the pro-inflammatory reactions that you see in autoimmune diseases,” he says. ▪