title: Longitudinal analysis of the human T cell response during acute hantavirus infection.
abstract: Longitudinal studies of T cell immune responses during viral infections in humans are essential for our understanding of how effector T cell responses develop, clear infection, and provide long-lasting immunity. Here, following an outbreak of a Puumala hantavirus infection in the human population, we longitudinally analyzed the primary CD8 T cell response in infected individuals from the first onset of clinical symptoms until viral clearance. A vigorous CD8 T cell response was observed early following the onset of clinical symptoms, determined by the presence of high numbers of Ki67(+)CD38(+)HLA-DR(+) effector CD8 T cells. This response encompassed up to 50% of total blood CD8 T cells, and it subsequently contracted in parallel with a decrease in viral load. Expression levels of perforin and granzyme B were high throughout the initial T cell response and likewise normalized following viral clearance. When monitoring regulatory components, no induction of regulatory CD4 or CD8 T cells was observed in the patients during the infection. However, CD8 as well as CD4 T cells exhibited a distinct expression profile of inhibitory PD-1 and CTLA-4 molecules. The present results provide insight into the development of the T cell response in humans, from the very onset of clinical symptoms following a viral infection to resolution of the disease.
authors.affiliation: Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors.forename: Therese
authors.initials: T
authors.lastname: Lindgren
authors.forename: Clas
authors.initials: C
authors.lastname: Ahlm
authors.forename: Nahla
authors.initials: N
authors.lastname: Mohamed
authors.forename: Magnus
authors.initials: M
authors.lastname: Evander
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Björkström
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D015703:Antigens, CD / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D060908:CTLA-4 Antigen; D015870:Gene Expression; D053804:Granzymes / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000032:analysis; D018778:Hantavirus Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008137:Longitudinal Studies; D008562:Membrane Glycoproteins / Q000032:analysis; D054353:Perforin / Q000096:biosynthesis; D061026:Programmed Cell Death 1 Receptor; D029262:Puumala virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054353:Perforin; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D053804:Granzymes