These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A triad of costimulatory molecules synergize to amplify T-cell activation.
    Author: Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MG, Schlom J.
    Journal: Cancer Res; 1999 Nov 15; 59(22):5800-7. PubMed ID: 10582702.
    Abstract:
    The activation of a T cell has been shown to require two signals via molecules present on professional antigen-presenting cells: signal 1, via a peptide/MHC complex; and signal 2, via a costimulatory molecule. Here, the role of three costimulatory molecules in the activation of T cells was examined. Poxvirus (vaccinia and avipox) vectors were used because of their ability to efficiently express multiple genes. Murine cells provided with signal 1 and infected with either recombinant vaccinia or avipox vectors containing a TRIad of COstimulatory Molecules (B7-1/ICAM-1/LFA-3, designated TRICOM) induced the activation of T cells to a far greater extent than cells infected with any one or two costimulatory molecules. Despite this T-cell "hyperstimulation" using TRICOM vectors, no evidence of apoptosis above that seen using the B7-1 vector was observed. Results using the TRICOM vectors were most dramatic under conditions of either low levels of first signal or low stimulator cell:T-cell ratios. Experiments using a four-gene construct also showed that TRICOM recombinants can enhance antigen-specific T-cell responses in vivo. These studies thus demonstrate for the first time the ability of vectors to introduce three costimulatory molecules into cells, thereby activating both CD4+ and CD8+ T-cell populations to levels greater than those achieved with the use of only one or two costimulatory molecules. This new threshold of T-cell activation has broad implications in vaccine design and development.
    [Abstract] [Full Text] [Related] [New Search]