Browsing by Subject "Costimulation"

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    Alternate costimulatory molecules in T cell activation: differential mechanisms for directing the immune response
    (Murcia : F. Hernández, 2003) Kohlmeier, J.E.; Benedict, S.H.
    T cells are required for an effective immune response against a wide range of pathogens and for the generation of immunological memory. T cell activation can be divided into two phases: an antigen-specific signal delivered through the T cell antigen receptor, and a costimulatory signal delivered through accessory molecules on the T cell surface. Following activation, T cells differentiate to acquire distinct effector functions depending on the costimulatory signal, cytokine environment, and the pathogen itself. Although CD28 has been identified as the dominant costimulatory molecule, several other molecules have been described as having a costimulatory function. This review will focus on recent evidence for the existence of alternate costimulatory molecules, and the differential roles they might play in the activation, development, and survival of T cells.
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    Differential requirements of naive and memory T cells for CD28 costimulation in autoimmune pathogenesis
    (Murcia : F. Hernández, 1999) Perrin, P.J.; Lovett-Rackez, A.; Phillips, S.M.; Racke, M.K.
    Experimental autoimmune encephalomyelitis (EAE) is the most extensively studied animal model of the human disease multiple sclerosis (MS). In EAE, CNS demyelination is induced by immunization with myelin proteins or adoptive transfer of myelin-reactive C D ~ +T cells. Since the antigen specificity of the immune response believed to be responsible for the pathology of MS is not well defined, therapies that target aspects of T cell activation that are not antigen specific may be more applicable to the treatment of MS. As a result, understanding the role of costimulatory molecules in the activation of nai've and memory T cells has become an area of extensive investigation. Naive T cells require two signals for activation. Signal one is provided by engagement of the T cell receptor (TCR) with MHCIpeptide complexes and provides antigen specificity to the immune response. The second signal, termed costimulation, is usually provided by B7 molecules on APC to CD28 molecules expressed on T cells and is antigen-independent. This review will discuss our current understanding of costimulation in the induction and perpetuation of EAE, as well as the potential of costimulaton blockade in the treatment of MS.