title: Cutting edge: cytotoxic granule polarization and cytolysis can occur without central supramolecular activation cluster formation in CD8+ effector T cells.
abstract: The functional implication of molecular segregation within the immunological synapse remains uncertain. We recently reported that effector but not naive TCR transgenic murine CD8+ T cells formed immunological synapses containing a central supramolecular activation cluster (cSMAC), suggesting that execution of effector functions such as cytolytic activity might be facilitated by the cSMAC structure. We have now explored this hypothesis using two approaches. First, by simultaneously imaging cSMAC formation and mobilization of cytotoxic granules to the synapse, we observed no correlation between the presence of a cSMAC and granule reorientation. Second, we took advantage of the observation that CD28 costimulation markedly enhances cSMAC formation. Granule polarization to the contact site was indistinguishable with B7-1+ and B7-1- target cells, and cytolytic activity against B7-1+ or B7-1- targets was similar and granule-dependent. Together, our results indicate that the formation of a cSMAC is not required for cytolytic activity in CD8+ effector T cells.
authors.affiliation: Committee on Cancer Biology, University of Chicago, IL 60637, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Keefe
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016764:Cell Polarity; D003594:Cytoplasmic Granules / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D053804:Granzymes; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000502:physiology; D012697:Serine Endopeptidases / Q000032:analysis; D000099221:Protein Kinase C zeta
chemical_list: D018122:B7-1 Antigen; D053804:Granzymes; D011493:Protein Kinase C; D012697:Serine Endopeptidases; D000099221:Protein Kinase C zeta