title: Granzyme B production distinguishes recently activated CD8(+) memory cells from resting memory cells.
abstract: For immune diagnostic purposes it would be critical to be able to distinguish between ongoing immune processes, such as active infections, and long-term immune memory, for example imprinted by infections that have been cleared a long time ago or by vaccinations. We tested the hypothesis that the secretion of granzyme B, as detected in ex vivo ELISPOT assays, permits this distinction. We studied EBV-, flu- and CMV-specific CD8(+) cells in healthy individuals, Vaccinia virus-reactive CD8(+) cells in the course of vaccination, and HIV-specific CD8(+) cells in HIV-infected individuals. Antigen-specific ex vivo GzB production was detected only transiently after Vaccinia immunization, and in HIV-infected individuals. Our data suggest that ex vivo ELISPOT measurements of granzyme B permit the identification of actively ongoing CD8(+) cell responses-a notion that is pertinent to the immune diagnostic of infections, transplantation, allergies, autoimmune diseases, tumors and vaccine development.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Nowacki
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
authors.forename: Wenji
authors.initials: W
authors.lastname: Zhang
authors.forename: Carey L
authors.initials: CL
authors.lastname: Shive
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kreher
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Paul V
authors.initials: PV
authors.lastname: Lehmann
authors.forename: Magdalena
authors.initials: M
authors.lastname: Tary-Lehmann
mesh_terms: D000328:Adult; D000917:Antibody Formation / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000737:chemistry / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D053804:Granzymes / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000502:physiology; D007156:Immunologic Memory / Q000276:immunology*; D066298:In Vitro Techniques; D007239:Infections / Q000097:blood / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014616:Vaccinia virus / Q000276:immunology