title: Human CD8+ CTL recognition and in vitro lysis of herpes simplex virus-infected cells by a non-MHC restricted mechanism.
abstract: Cytotoxic T lymphocytes (CTL) are important for the recognition and lysis of virally infected cells, but their effectiveness can be limited by viral immune evasion mechanisms. We investigated the immunophenotype and function of human CD8+ T cells raised in response to herpes simplex virus (HSV). The expanded population contained cells of an activated and mature phenotype, as determined by the expressions of CD25, CD45RO, CD57, CD95 and HLA-DR. Cultured cells also expressed CD45RA. These cells lysed autologous and allogeneic HSV-infected lymphoblastoid cell line (LCL) targets via a non-major histocompatibility complex (MHC) restricted recognition pathway. Inhibition assays showed the mechanism of cytotoxicity to be calcium-dependent, granule exocytosis pathway, rather than the internal disintegration pathway. Cold target competition assays indicated that a common CTL population contributed to the recognition of autologous and allogeneic-infected targets. These effectors showed recognition of infected targets which was distinct from that of K562 cells. Non-MHC restricted lysis-associated molecule 2B4 (CD244) was upregulated on culturing and made a significant contribution to lysis of FcgammaR-bearing targets in a redirected killing assay. These findings suggest that CTL can recognize virally infected cells through a combination of non-MHC restricted mechanisms and may result in more efficient lysis than classical CD8+ T cells.
authors.affiliation: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK. R.Garland@bristol.ac.uk
authors.forename: R J
authors.initials: RJ
authors.lastname: Garland
authors.forename: N
authors.initials: N
authors.lastname: El-Shanti
authors.forename: S E
authors.initials: SE
authors.lastname: West
authors.forename: J P
authors.initials: JP
authors.lastname: Hancock
authors.forename: N J
authors.initials: NJ
authors.lastname: Goulden
authors.forename: C G
authors.initials: CG
authors.lastname: Steward
authors.forename: A W
authors.initials: AW
authors.lastname: Rowbottom
mesh_terms: D015703:Antigens, CD; D017252:CD3 Complex / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005089:Exocytosis; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000378:metabolism; D010641:Phenotype; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D017252:CD3 Complex; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family