The development of T cells involves the differentiation of a common precursor cell into either an alpha/beta (ab) or gamma/delta (gd) lineage T cell, initiating a program of maturation which results in phenotypically and functionally distinct T cells. The overall focus of my project is to examine the pathways and genes governing human ab/gd T cell lineage commitment. First, I will determine the role of T cell receptor (TCR) gene rearrangements in ab/gd lineage commitment using two approaches: a novel quantitative Southern blotting method that I will develop, and PCR-RFLP analysis. I will analyze the rearrangement of b-TCR genes in gd cells and g+d TCR genes in ab T cells and use these data to formulate a model for the role of TCR genes in human ab/gd T cell commitment. Secondly, I will functionally evaluate the lineage potential of discrete populations of cells to become either ab or gd T cells in an in vitro fetal thymic organ culture system. These studies will identify the point of lineage divergence for ab/gd cell development and the phenotypes of the bipotent vs. committed precursors. In summary, my analysis of TCR genes will yield new information regarding the role of T cell receptor rearrangements in the ab/gd lineage decision during human thymopoiesis. Additionally, a functional evaluation of the developmental potential of defined thymocyte populations will pinpoint when lineage commitment occurs, facilitating future cDNA array studies of the gene expression changes happening during this process.
| Joachims, Michelle L; Marble, Patrick A; Laurent, Aletha B et al. (2008) Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases. J Immunol 181:8153-61 |
| Joachims, Michelle L; Chain, Jennifer L; Hooker, Scott W et al. (2006) Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements, intracellular TCR beta expression, and gamma delta developmental potential--differences between men and mice. J Immunol 176:1543-52 |
| Chain, J L; Joachims, M L; Hooker, S W et al. (2005) Real-time PCR method for the quantitative analysis of human T-cell receptor gamma and beta gene rearrangements. J Immunol Methods 300:12-23 |
