doi: 10.3389/fimmu.2014.00411 Revisiting thymus function

For centuries, the thymus has been an organ in search of a function. The fact that it is a large mass of tissue in infancy was not appreciated at the beginning of the twentieth Century, as autopsies per-formed in infants succumbing to fatal ill-nesses such as diphtheria, revealed a small thymus. This resulted from stress during the illness, but the small size of the thy-mus was thought to be the norm. When infant death occurred during anesthesia for stress-unrelated conditions, fatality was blamed not on the anesthetic but on the large thymus. Some doctors even pre-scribed radiation therapy to shrink the thy-mus (1), not realizing that some of their patients would later develop adenocarci-noma of the thyroid. Prior to 1961, the thymus was con-sidered not to have any role in immu-nity. The major reasons for this can be summed up as follows. Unlike lympho-cytes obtained by thoracic duct cannu-lation or from spleen and lymph nodes, thymus lymphocytes were generally poor in their ability to initiate immune reac-tions after adoptive transfer to appropri-ate recipients. Thoracic duct lymphocytes could home from blood into lymphoid tis-sues, “the only exception ” being “the thy-mus in which very few small lymphocytes” appeared “to lodge ” (2). The production of antibody-forming plasma cells and the for-mation of germinal centers, so prominent in spleen and lymph nodes, were not seen in thymus tissue of normal or immunized animals. Defects in immune responsive-ness had never been documented in mice whose thymuses had been removed dur-ing adult life, a fact that had led some groups to conclude that “the thymus gland does not participate in the control of the immune response ” (3). At a Symposiu