Immune Senescence and Reconstitution

The Laboratory of T-Cell Biology and Immune Reconstitution is led by Gregory D. Sempowski, PhD and is located in the Regional Biocontainment Building at Duke. The Sempowski lab has an independent research program studying immune senescence associated with aging and works collaboratively with investigators from Duke, UNC Chapel Hill, Memorial Sloan Kettering, University of Georgia, University of Arizona and the Radiation Effect Research Foundation (Hiroshima, Japan). The Laboratory of T-Cell Biology and Immune Reconstitution is also home to two DHVI Shared Resource Facilities which are supported by NIAID Core grants.

Immune Senescence and T Cell Reconstitution

The Sempowski lab is primarily focused on developing strategies to enhance T cell reconstitution in order to offset thymic immune depletion due to immunodeficiency associated with aging, stress, or illness. The thymus plays an important role in maintaining the peripheral T cell pool in children and adults. As the thymus gets smaller with age, it produces significantly lower amounts of T cells resulting in an overall reduced immune response in older individuals. Currently, there are no treatments available to protect against aging, stress or illness-related thymic atrophy or accelerate recovery, thus leaving the immune system compromised. The Sempowski group is working to define the mechanisms that drive thymic involution and find ways of blocking or reversing thymic involution in order to enhance host response in at-risk populations against potential natural or man-made biothreats. The lab has identified the IL-6 cytokine gene family (i.e., leukemia inhibitory factor, IL-6, and oncostatin M) as thymosuppressive agents by the observation that they can acutely involute the thymus when injected into a young, healthy mouse. They also have identified leptin as a novel, thymostimulatory agent that can protect against stress-induced acute thymic atrophy. Identified hormones, cytokines and inhibitors of cytokine receptors are being tested as possible strategies to stimulate thymopoiesis and T cell reconstitution in mouse models of vaccination and infectious challenge.

Effects of Radiation and Aging on the Human Immune System

The Sempowski lab is part of an international consortium of nine labs funded by NIAID to study the effects of atomic bomb radiation and aging on the human immune system. Investigators in both the United States and Japan are systematically analyzing biological samples from the unique population of elderly Japanese atomic bomb survivors to better understand the health consequences of exposure to ionizing radiation on the natural aging process.

SE STI CRC - Immunology Component

The Southeast Sexually Transmitted Infection Cooperative Research Center (SE STI CRC) based at UNC Chapel Hill supports an Immunology component based in the Sempowski lab in collaboration with Dr. Herman Staats (Duke, Pathology). This center component provides expertise in systemic and mucosal immunity with an emphasis on humoral, cellular and biomarker analysis. This new component of the SE STI center in 2009 was included to provide mechanistic study of innate and adaptive immune response to N. gonorrhoeae or experimental vaccination for N. gonorrhoeae.

Shared Resource Facilities

Lastly, the Sempowski laboratory contains a service component consisting of the Immune Reconstitution & Biomarker Analysis Shared Resource and the Biocontainment Animal Imaging Shared Resource. The IR & Biomarker Analysis facility provides access to specialized instrumentation for Real-Time qPCR and Luminex bead-based multiplex assays, and runs molecular assays to monitor thymic output in mouse, human and non-human primate samples. This facility provides the patented Mouse TREC Assay, which is performed regularly for investigators from all over the world. This assay has proven invaluable for monitoring thymopoiesis in mice. The Biocontainment Animal Imaging facility is housed in an animal Biocontainment suite in the Regional Biocontainment Building at Duke. The facility has a state-of-the-art Xenogen Spectrum in vivo imaging system capable of noninvasive quantitative 3D molecular imaging of anesthetized mice, rats, rabbits and guinea pigs. The instrument can quantify bioluminescence and fluorescence (490-850nm). Ongoing research applications include: poxvirus gene expression, replication, and vaccine development, viral vector-based vaccine delivery and efficacy, and in vivo tracking of novel vaccine components with fluorescent tags.

SERCEB - Flow, Biomarker and Imaging Core

The Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB) supports a BSL3 Host Pathogen Interaction Core (FBI Core). This Core is comprised of technologies and services offered through the NIAID-funded Regional Biocontainment Laboratory at Duke in conjunction with DHVI shared resource facilities. This BSL3 SERCEB Core routinely provides investigators with high-quality flow cytometry, in vivo imaging, protein array analysis, and complete blood count/hematologic analysis for their basic and applied biodefense and emerging infectious disease research efforts.

RadCCORE - Immune Monitoring Core

The Radiation Countermeasures Center of Research Excellence (RadCCORE) based at Duke supports an Immune Monitoring Core comprised of technologies and services offered by two service laboratories within the Duke Human Vaccine Institute (DHVI): the Flow Cytometry Facility and the Immune Reconstitution and Biomarker Facility. The Immune Monitoring Core centrally provides RadCCORE investigators with high quality, state-of-the-art cell sorting, multiplex cytokine/chemokine assays, and T cell receptor gene expression analysis for their basic and applied research efforts.