Lineage Diversion of T Cell Receptor Transgenic Thymocytes Revealed by Lineage Fate Mapping

Background: The binding of the T cell receptor (TCR) to major histocompatibility complex (MHC) molecules in the thymus determines fates of $TCR\alpha\beta$ lymphocytes that subsequently home to secondary lymphoid tissue. TCR transgenic models have been used to study thymic selection and lineage commitment. Most TCR transgenic mice express the rearranged $TCR\alpha\beta$ prematurely at the double negative stage and abnormal TCRαβ populations of T cells that are not easily detected in non-transgenic mice have been found in secondary lymphoid tissue of TCR transgenic mice. Methodology and Principal Findings: To determine developmental pathways of TCR-transgenic thymocytes, we used Cre-LoxP-mediated fate mapping and show here that premature expression of a transgenic $TCR\alpha\beta$ diverts some developing thymocytes to a developmental pathway which resembles that of gamma delta cells. We found that most peripheral T cells with the HY-TCR in male mice have bypassed the RORγt-positive $CD4^{+}8^{+}$ (double positive, DP) stage to accumulate either as $CD4^{-}8^{-}$ (double negative, DN) or as $CD8\alpha^{+}$ T cells in lymph nodes or gut epithelium. Likewise, DN $TCR\alpha\beta$ cells in lymphoid tissue of female mice were not derived from DP thymocytes. Conclusion: The results further support the hypothesis that the premature expression of the $TCR\alpha\beta$ can divert DN thymocytes into gamma delta lineage cells

Numerical Modelling Of The V-J Combinations Of The T Cell Receptor TRA/TRD Locus

T-Cell antigen Receptor (TR) repertoire is generated through rearrangements of V and J genes encoding α and β chains. The quantification and frequency for every V-J combination during ontogeny and development of the immune system remain to be precisely established. We have addressed this issue by building a model able to account for Vα-Jα gene rearrangements during thymus development of mice. So we developed a numerical model on the whole TRA/TRD locus, based on experimental data, to estimate how Vα and Jα genes become accessible to rearrangements. The progressive opening of the locus to V-J gene recombinations is modeled through windows of accessibility of different sizes and with different speeds of progression. Furthermore, the possibility of successive secondary V-J rearrangements was included in the modelling. The model points out some unbalanced V-J associations resulting from a preferential access to gene rearrangements and from a non-uniform partition of the accessibility of the J genes, depending on their location in the locus. The model shows that 3 to 4 successive rearrangements are sufficient to explain the use of all the V and J genes of the locus. Finally, the model provides information on both the kinetics of rearrangements and frequencies of each V-J associations. The model accounts for the essential features of the observed rearrangements on the TRA/TRD locus and may provide a reference for the repertoire of the V-J combinatorial diversity

Political Economy of Civil Society

This chapter explores the role of civil society in relation to the economy and the polity by focusing on three distinct yet related dimensions: (1) the conceptual history of civil society in relation to political economy; (2) the theory underpinning a political economy of civil society; (3) the implications of a political economy of civil society for policy-making. The main argument is that there is a fundamental difference between ancient and medieval conceptions, which emphasise natural sociability, and modern accounts that accentuate a violent ‘state of nature’. As a result, civil society either reflects the fundamental embeddedness of economic and political processes in social relations or is an artificial construct. The chapter develops a typology of four modern models, provides a theory of the political economy of civil society and outlines a series of policy ideas

Energy dissipation effects on imaging of soft materials by dynamic atomic force microscopy: A DNA-chip study

International audienc

AN AFM INVESTIGATION OF SURFACE ENERGY OF PENTACENE FILMS ON PARYLENE-C AND BENZOCYCLOBUTENE

International audienc