In children, the thymus plays a central role in generating T-cells that are a key component of the immune system. In adults, the thymus is likely involved in regenerating T-cells after T-cells are depleted by chemotherapy, bone marrow transplantation and infection with Human Immunodeficiency Virus (HIV). Thus, understanding the factors and cells that influence T-cell regeneration and how it can be improved in those conditions is a major goal of Dr. Christel Uittenbogaart's research.
The focus of the laboratory is to elucidate factors such as chemokines and cytokines involved in thymopoiesis that can be exploited to boost T-cell developmental processes; investigate the function of intrathymic dendritic cells such as plasmacytoid dendritic cells, the natural Interferon-alpha (IFN-alpha) producing cells, and myeloid dendritic cells in normal T-cell development; evaluate the mechanism of the immunosuppressive effects of high levels of IFN-alpha observed in certain diseases; and examine the cytopathicity, replicative capacity, and cell tropism of various pediatric HIV isolates in the thymus. The researchers utilize three different model systems to study T-cell development: in vitro thymocyte suspension culture, thymus organ culture and human thymus grafts in the SCID-hu mouse.
The goal of Uittenbogaart's research is to gain a better understanding of the development and function of the immune system in order to facilitate the development and design of novel therapeutic approaches to immunodeficiency such as observed after chemotherapy, bone marrow transplantation and in HIV disease.
Pedroza-Martins L, Boscardin WJ, Anisman-Posner DJ, Redsar BN, Bryson YJ, Yang OO, Uittenbogaart CH. Interferon-gamma decreases replication of primary R5 HIV-1 isolates in thymocytes. AIDS. 2006; 20(6): 939-42.
Yang OO, Lin H, Dagarag M, Ng HL, Effros RB, Uittenbogaart CH. Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes. Virology. 2005; 332(1): 16-9.
Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, Wijnands E, Blom B, Spits H. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. Blood. 2004; 104(13): 3886-93.
Gurney KB, Colantonio AD, Blom B, Spits H, Uittenbogaart CH. Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection. J Immunol. 2004; 173(12): 7269-76.
Lubong R, Ng HL, Uittenbogaart CH, Yang OO. Culturing of HIV-1-specific cytotoxic T lymphocytes with interleukin-7 and interleukin-15. Virology. 2004; 325(2): 175-80.