Researchers find cervical thymus that produces T cells and mounts antibody response
By Melissa Lee Phillips | March 3, 2006
Wild-type laboratory mice possess a functional second thymus located in the neck, according to a report in this week's Science Express. The finding may influence interpretations of previous studies of the immune system in mice thought to possess no thymus, according to the senior author.
Because experiments have revealed T cell development in mice whose thymus has been removed, some researchers have suggested that T cells may develop in the skin or the gut, Hans-Reimer Rodewald of the University of Ulm in Germany told The Scientist. "Some of this that was considered extra-thymic T cell development may have taken place in the second thymus."
Fish and birds possess cervical thymi, Rodewald said, and a cervical thymus has been reported in human fetuses, but its presence in humans after birth is rare and usually associated with pathology. In 1962, a group reported tissue resembling a thymus in mouse neck, Rodewald said, but, "for reasons that are not clear to me, this had never been followed up or taken into consideration."
According to Dan Littman of New York University, who was not involved in the study, "most people just assumed that there were lymph nodes there."
During experiments on thymus development, Rodewald's group -- led by Grzegorz Terszowski and Susanna M. Müller, also of the University of Ulm -- noticed several tissues in the mouse neck that had lymphoid characteristics but couldn't be definitively identified as lymph nodes.
Instead, the scientists found that the architecture of these tissues resembled the thymus. They also found that this tissue expressed several thymus-specific genes. The researchers engineered mice to express green fluorescent protein under control of a thymus-specific transcription factor. Between 50% and 90% of examined mice had at least one cervical thymus, depending on their genetic background, and some had two or three.
Rodewald and his colleagues then conducted a series of transplantation studies to see if the cervical thymus could support normal T cell development. When they grafted a cervical thymus into a mouse with no thymus, they found that progenitor T cells from the host colonized the transplanted organ. Mice that received transplants showed thymus-derived T cells in their blood by eight weeks after the procedures. Also, when the researchers immunized the mice with hepatitis B antigen, they found that only the mice with a transplanted cervical thymus showed a significant antibody response.
The discovery of a functional cervical thymus in mice is "not totally unexpected," NYU's Littman said, but "it's the first systematic analysis showing that these are not just occasional ectopic clusters of thymic-like tissue, but rather that these are structures that develop normally in most animals."
The study's novel finding is that the cervical thymus "generates T cells in much the same way as the thoracic" thymus, according to Jacques Miller of The Walter and Eliza Hall Institute of Medical Research in Australia, who did not participate in the research. This was "hardly unexpected but had to be proven."
Skin graft rejection experiments in mice with a transplanted cervical thymus would have added to the study, Miller told The Scientist in an Email: "Such rejection is an exquisitely sensitive way of determining restoration of immune competence."
Littman agreed that the new results may help to explain studies that have shown the adaptive immune system can continue to function even after removal of the thymus. "These experiments have been interpreted as indicating that there's differentiation of T cells in the absence of thymus in the periphery," he told The Scientist, but "some of those experiments may very well be explained by the presence of these structures."
Melissa Lee Phillips
Links within this article
T. Toma, "A new mechanism of thymic selection," The Scientist, April 4, 2001.
G. Terszowski et al., "Evidence for a functional second thymus in mice," Science, published online March 2, 2006.
D. F. Tough, J. Sprent, "Turnover of naïve- and memory-phenotype T cells," Journal of Experimental Medicine, April 1, 1994.
J. P. Roberts, "T-Cell subsets: On the immunity warpath," The Scientist, May 5, 2003.
D. A. Loney, N. M. Bauman, "Ectopic cervical thymic masses in infants: a case report and review of the literature," International Journal of Pediatric Otorhinolaryngology , February 1998.