Denise Faustman, M.D., Ph.D., Director of the Immunobiology Laboratory at Massachusetts General Hospital, is researching "Apoptosis in the Thymus and Periphery." Dr. Faustman gives the following description of her research project:

     "Education to self in all mammals occurs in the thymus, an organ in the chest, as well as in T cell education in the peripheral blood and tissues. The two different sites for education are commonly referred to as central versus peripheral tolerance. Many "bad" T cells are produced; but in non-autoimmune states, these cells are selected or killed by an accelerated cell death process called apoptosis.

     "It is our belief, as well as others, but not all scientists, that defective apoptosis may be related to autoimmune disease. In this pilot study, we will try to prove in the NOD mouse that the recently described "bad" T cell population in the thymus is lineage related to the "bad" T cell population we have recently found in the periphery. To prove these two cells are the same would help to unify the scientific field of how T cells, across the life span, as juvenile delinquents (thymus cells/central tolerance) as well as convicted criminals mature (mature cells/peripheral tolerance) destroy self tissues."

     David Beller, Ph.D., Professor of Medicine at the Boston University Medical Campus, is studying the "Molecular Regulation of IL-12 Dysfunction in Autoimmunity." He describes his study:

     "All individuals harbor autoreactive lymphocytes, immune cells capable of being activated by proteins our bodies naturally produce. Autoimmunity results from a failure to control these ubiquitous, potentially harmful cells. However, it is not clear why autoimmunity usually takes one of two general forms: B lymphocyte-mediated systemic diseases like lupus, or T [thymus] cell mediated organ specific diseases, like diabetes. it is reasonable to expect than an understanding of how the "anti-self immune response is tipped towards one of these two pathways will provide key insights into the basic mechanisms controlling autoimmunity.

     "We have postulated that the defects responsible for these events involve the basic language of communication within the immune system, hormone-like mediators referred to as cytokines. Our studies have focused on cells of the innate immune system (macrophages and dendritic cells) known to contribute to immune regulation through cytokine production. Substantial cytokine dysregulation by these cells is an early event in mouse models of both systemic and organ specific autoimmunity, always preceding expression of disease signs.

     "The cytokine IL-12 is known to be involved in the cellular events that favor organ specific autoimmunity. We have found that macrophages and dendritic cells from lupus-prone mice produce very little IL-12 (thus favoring systemic autoimmunity). Macrophages and dendritic cells from diabetes- or MS-prone mice, in contrast, make far more IL-12 than any normal mice, potentially predisposing to organ specific disease. Thus, this intrinsic pattern of IL-12 production may help explain a critical facet of autoimmunity.

     "The role of IL-12 in the development of autoimmunity will be tested in this proposal, by focusing on (i) the role of this cytokine, and the cells that produce it, in the control of B and T lymphocyte function and (ii) the molecular mechanism that accounts for its aberrant production in all autoimmune-prone mice tested."

      We in AARDA are excited by the possible outcomes of these research projects, and we look forward to making further reports to our members.