David Parker, Ph.D.
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- Phone:
- 503 494-1498
Background
Dr. Parker’s laboratory is interested in the cell-surface molecules and intracellular signaling pathways which determine whether an encounter between helper T cells and B cells or other antigen presenting cells results in immunity or tolerance. In a simplified model of peripheral tolerance to self, we found that a signal through OX40 (CD134) blocks functional anergy in transferred T cells responding to transgenic or allogeneic antigens, drives the T cells to differentiate into cytokine-secreting effector cells and results in fatal acute graft versus host disease in unirradiated recipient animals. Current work is focused on the role of the alternative pathway of NFkB activation in that model. In a second project, the lab is exploring the possibility that certain subsets of weakly autoreactive B cells play an essential role as antigen-presenting cells in inducing tolerance to self antigens in T cells. In a third project, we are exploring the "immunological synapse," the structure that forms in the contact zone between a T cell and an antigen presenting cell. We are examining the role of the synapse in the specific delivery of effector cytokines from T cells to antigen presenting cells, with an emphasis on the membrane-bound TNF family members, CD40L (CD154) and FasL. We are also exploring differences among T cell subsets in the structure of the synapse and the functional consequences of those differences.
Selected Publications
"B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells,"
"Preformed CD40L is stored in Th1, Th2, Th17, and T follicular helper cells as well as CD4 +8 - thymocytes and invariant NKT cells but not in Treg cells,"
"NF-κB-inducing kinase plays an essential T cell-intrinsic role in graft-versus-host disease and lethal autoimmunity in mice,"
"Cyclosporine-resistant, Rab27a-independent mobilization of intracellular preformed CD40 ligand mediates antigen-specific T cell help in vitro,"
"The 50th midwinter conference of immunologists at asilomar,"
