Thymus

DHVI investigators have made major contributions in the area of human immune system reconstitution. Drs. M. Louise Markert and Barton F. Haynes have developed a creative strategy for reconstitution of the immune system in DiGeorge syndrome, a disease in which the thymus fails to develop. This congenital abnormality found in approximately 1 in 250 infants was once considered a fatal disease. Drs. Markert and Haynes pioneered the development of thymus transplantation, giving hope to parents of infants with the syndrome. So far, over 25 infants have received thymus transplants, with the survival rate around 70%. Work in this program has broadened the understanding of DiGeorge syndrome, in particular showing that infants do not have to have 22q11 hemizygosity to have this condition. Discoveries have included a new phenotype that can develop in infants with complete DiGeorge syndrome, one in which oligoclonal T cells develop, infiltrating the skin and leading to rash and lymphadenopathy.

Dr. Greg Sempowski’s research is focused on the other end of the human life span, that of T cell production and immune responses in the aging adult. The thymus is a complex organ responsible for the maturation and education of peripheral T cells. Production of broadly reactive T cells and maintenance of a diverse peripheral T cell repertoire are critical to the success of the human immune system. Unfortunately, thymopoiesis is attenuated by normal aging. As an individual ages, the thymus involutes by unknown mechanisms and output of new T cells significantly falls. Loss of a broadly reactive naive peripheral T cell repertoire with age results in suppressed immune responses to infections and vaccines in adults. The overall goal of Dr. Sempowski¹s research is to define critical factors and pathways involved in thymus tissue aging, and be poised to translate newly-defined therapeutic strategies to humans for improved T cell reconstitution and immunity in a variety of clinical settings. His work is critical to improving the effective response to vaccines in older individuals.