Potential roles for CD8(+) T cells in rheumatoid arthritis

CD8(+) T cells have long been suggested to play a role in rheumatoid arthritis (RA). The current paradigm on the pathogenesis and maintenance of the disease would endorse these cells with predominantly protective and minor influences. However, several animal studies suggest that these cells may have a predominantly proinflammatory (cytotoxic) effect in the disease. Other studies claim otherwise, that they have a mainly regulatory role in inflammatory joints. The evidence in human disease is remarkably scarce. Studies in human samples indicate that CD8(+) T cells play an important role in the establishment of germinal centers observed in nearly 50% of RA patients, which may have a decisive role in the initiation and maintenance of the disease process. The conflicting results of experimental studies, the scarcity of data and the complexity of research needed to unravel these complex interactions may explain the relative oblivion of CD8 cells in the field of arthritis over recent decades. Is this a wise decision or may we run the risk of not finding the key to RA because we search for it where there is light as opposed to its probable location? The present review brings together available data on the potential role of CD8(+) T cells in inflammation, with emphasis on rheumatoid arthritis, hoping to foster interest and fresh research in this area.