Jonathan M. Green, M.D.

DEPARTMENT OF Internal Medicine
Keywords: immunology, lymphocyte, costimulation, CD28, CD43

The focus of my laboratory is to understand the role of accessory molecules on the surface of T lymphocytes in modulating the T cells response to antigen, and how these proteins influence susceptibility to disease. T cell recognition of antigen occurs through the interaction of the T cell receptor with an antigen-MHC complex. However, accessory proteins play critical roles in modulating both the initial responses to antigen as well differentiation into phenotypically distinct effector cells.

The importance of CD28 in T cell activation has been well documented; however, the mechanism by which CD28 regulates T cells remains controversial. We are currently exploring the biochemical basis for CD28 function using retroviral gene transfer into primary T cells. Studies with CD28-deficient mice and "CD28 knock-in" expressing specific mutant forms of CD28, provide for the ability to determine the precise determinants of CD28 function both in vitro and in vivo. CD28-deficient mice have some defects in T cell function, but in many respects are similar to wild type. However, mice deficient in both CD2 and CD28 are profoundly immunosuppressed, manifesting susceptibility to opportunistic infection and other diseases. Studies in the lab are ongoing to determine the specific immunologic defects in the CD2/CD28-double deficient mice that lead to disease.

Additional members of the B7:CD28 family have been shown to inhibit T cell function. Thus, both the intiation and termination of T cell directed immune responses are regulated by this family of receptors. New studies in the lab are directed at elucidating how the balance of these signals determine the outcome of inflammation in vivo.

Another accessory protein of interest to the lab is CD43. CD43 is a large, mucin-like protein which is highly expressed on T cells. It has been speculated that it may function by preventing intercellular contact by way of it’s large negative charge and overall structure. We are currently investigating the role of CD43 in the formation of the immunologic synapse, and the function of the cytoplasmic domain of CD43 in T cell activation and effector function.