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Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure▿ †

By Alexandre Harari, Felicitas Bellutti Enders, Cristina Cellerai, Pierre-Alexandre Bart and Giuseppe Pantaleo

Abstract

Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin− GrmB− GrmA+/− GrmK+; in CMV-specific cells, it was perforin+ GrmB+ GrmA+ GrmK−/+; and in EBV- and HIV-1-specific cells, it was perforin−/+ GrmB+ GrmA+ GrmK+. On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK+ profile was associated with early-stage memory CD8 T-cell differentiation, the perforin+ GrmB+ GrmA+ profile with advanced-stage differentiation, and the GrmB+ GrmA+ Grmk+ profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure

Topics: Pathogenesis and Immunity
Publisher: American Society for Microbiology (ASM)
OAI identifier: oai:pubmedcentral.nih.gov:2655574
Provided by: PubMed Central
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