Mandy Ford, PhD - Basic Science Research Faculty

Mandy Ford, PhD

Assistant Professor
Department of Surgery
Emory University School of Medicine

A major challenge in the field of organ and tissue transplantation is inhibiting the vigorous immune response orchestrated by donor-specific CD4 + and CD8 + T cells. These cells become activated after recognizing alloantigens and receiving appropriate costimulatory signals, including those transduced through the CD28/B7 and CD40/CD154 pathways. One promising therapy designed to regulate the immune response to donor tissue involves the use of reagents designed to block the costimulatory molecules required for T cell activation.

The goal of my research is to use transgenic systems with defined alloantigens to carefully dissect the factors necessary to induce and maintain the state of costimulation blockade-induced tolerance. Specifically, we are focused on four different parameters, which independently impact the fate and function of donor-specific T cells.

  1. First, we are investigating the role of donor-reactive CD4 + and CD8 + T cell precursor frequency as a critical factor affecting the degree of T cell proliferation, acquisition of effector function, and requirement for costimulatory signals during allograft rejection or acceptance.  
  2. Secondly, as a corollary to this work, we are interested in defining the effect of the degree of antigenic exposure of donor-specific T cells on the efficacy of costimulation blockade as a means to induce transplant tolerance.  
  3. Third, we are examining the impact of stimulation history (i.e. naïve versus memory T cells) on the susceptibility of donor-reactive T cells to costimulation blockade-induced tolerance. Finally, we are interested in studying the impact of TCR affinity for peptide:MHC ligand in the susceptibility of T cells to CD28 and CD154 blockade. Understanding the relative influence of these four parameters on donor-reactive T cell activation and differentiation has broad implications for the development of strategies to inhibit these responses.

Recent Publications (2006-2007)

  • Ford ML, Koehn BH, Wagener ME, Jiang W, Gangappa S, Pearson TC, Larsen CP. 2007. Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation. J. Exp. Med. 204 (2): 299-309.  
  • Ford ML, Wagener ME, Gangappa S, Pearson TC, Larsen CP. 2007. Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Am. J Transplant . 7: 1-11.  
  • Ford, ML and Evavold, BD. 2006. Modulation of MOG 37-50-specific CD8 + T cell activation and expansion by CD43. Cellular Immunology. 240:53-61.