MHC‐Linked Syngeneic Developmental Preference inThymic Lobes Colonized with Bone Marrow Cells: A Mathematical model

Abstract

Reconstitution of the T-cell compartment after bone marrow transplantation depends on successful colonization of the thymus by bone-marrow-derived progenitor cells. Recent studies compared the development of syngeneic and allogeneic bone-marrow-derived cells in cocultures with lymphoid-depleted fetal thymus explants, leading to the discovery of MHC-linked syngeneic developmental preference (SDP) in the thymus. To determine the nature of cell interactions among the bone marrow and thymic elements that might underlie SDP, we analyzed this phenomenon by mathematical modeling. The results indicate that syngeneic mature T cells, responsible for inducing this preference, probably interfere both with the seeding of allogeneic bone-marrow-derived thymocyte progenitors in the thymic stroma and with their subsequent proliferation. In addition, the possibility of augmented death among the developing allogeneic thymocytes cannot be ruled out.

Understanding natural killer cell regulation by mathematical approaches

“…The latter (and other so-called “Monte Carlo” modeling methods, such as stochastic agent-based models – see below) have been developed to better account for intrinsic cellular and molecular fluctuations. For example, see our (mostly ODE) models of lymphocyte development – T cell development in the thymus (Mehr et al, 1993, 1994, 1995, 1996a,b, 1997, 1998) and homeostasis in peripheral blood (Mehr and Perelson, 1997), and ODE or hybrid models of B cell development and responses (Mehr et al, 2003; Shahaf et al, 2004, 2006, 2010). Stochastic modeling has also been extensively used by several groups, e.g., the Hodgkin group’s “Cyton” model (Lee et al, 2009; Markham et al, 2010; Duffy and Hodgkin, 2012; Duffy et al, 2012).…”

Models and methods for analysis of lymphocyte repertoire generation, development, selection and evolution

“…Our favorite example is that of models of lymphocyte development -T cell development in the thymus [99][100][101][102][103][104][105] and homeostasis in peripheral blood [106], and B cell [107][108][109][110] and NK cell (our work in progress) development in the bone marrow and peripheral lymphoid tissues. In many of these and similar studies, the dynamics of developing cell populations are elucidated using BrdU and other methods of labeling dividing cells.…”

A Monte Carlo Simulation for the Construction of Cytotoxic T Lymphocytes Repertoire

“…Another equation-based model was used to to compare the intrathymic development of bone marrow precursors, derived either from young or old donors (Mehr et al, 1993). In Mehr et al (1998) the phenomenon of MHC-linked syngeneic developmental preference was analyzed by a mathematical model. In another study, the authors focused on the naïve T-cell compartment defined by the presence of T-cell receptors excision circles formed during T-cell receptor gene rearrangement (Hazenberg et al, 2000).…”