Chemokines orchestrate more than migration for immune cells

Scientists have discovered that chemical signals thought to function primarily as cellular traffic directors play a much more complex role in the activation of the adaptive immune response than was previously expected. The research, published in the April issue of Immunity, demonstrates that the molecules belonging to a class of proteins called chemokines do more than simply guide migration of the immune cells that are activated in the very early stages of infection.

Dendritic cells (DCs) are present in tissues that are closely associated with the external environment. DCs function as a kind of sentinel for the immune system, constantly sampling their surroundings for potentially harmful pathogens. Once they encounter a bacteria or virus, the DCs mature and migrate from the periphery to lymphoid tissues where they activate T cells, critical immune cells that are essential to the immune response.

Chemokines are molecules that have been shown to direct the migration of DCs and recent research has indicated that they may also play a role in DC maturation. Dr. Martin F. Bachman from Cytos Biotechnology in Switzerland and colleagues were interested in identifying new proteins that might indirectly govern T cell responses through activation of DCs.

The researchers found that the chemokines CCL19 and CCL21 induced maturation of activated DCs and a subsequent upregulation of potent stimulatory molecules that enhanced T cell proliferation. Mice that lack CCL19/CCL21 had only partially activated DCs even when the DCs were activated by pathogen signals, suggesting that the chemokines are required for full maturation of DCs and proper activation of T cells.

“These findings indicate that induction of DC maturation is an important property of CCL19/CCL21 and suggest that chemokines may not only organize the migration of DCs but also directly regulate their ability to prime T cell responses,” writes Dr. Bachmann. A clear understanding of the influence of these chemokines on T cell immune responses will be useful for rational design of future antiviral and anticancer therapies.