Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses.
The number of naive T cells decreases and susceptibility to new microbial infections increases with age. Here we describe a previously unknown subset of phenotypically naive human CD8(+) T cells that rapidly secreted multiple cytokines in response to persistent viral antigens but differed transcriptionally from memory and effector T cells. The frequency of these CD8(+) T cells, called 'memory T cells with a naive phenotype' (TMNP cells), increased with age and after severe acute infection and inversely correlated with the residual capacity of the immune system to respond to new infections with age. CD8(+) TMNP cells represent a potential new target for the immunotherapy of persistent infections and should be accounted for and subtracted from the naive pool if truly naive T cells are needed to respond to antigens.
Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Arizona, USA.
Vesna
V
Pulko
Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Arizona, USA.
John S
0000-0002-9482-1066
JS
Davies
Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Arizona, USA.
Carmine
C
Martinez
Blood Systems Research Institute, San Francisco, California, USA.
Marion C
MC
Lanteri
Blood Systems Research Institute, San Francisco, California, USA.
Michael P
MP
Busch
Department of Medicine, Washington University, St. Louis, Missouri, USA.|Department of Molecular Microbiology, Washington University, St. Louis, Missouri, USA.|Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA.
Michael S
MS
Diamond
Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA.|Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA.
Kenneth
K
Knox
Department of Systems Biology, Columbia University Medical Center, New York, New York, USA.
Erin C
EC
Bush
Department of Systems Biology, Columbia University Medical Center, New York, New York, USA.|Department of Biochemistry &Molecular Biophysics, Columbia University Medical Center, New York, New York, USA.|Sulzburger Columbia Genome Center, Columbia University Medical Center, New York, New York, USA.
Peter A
PA
Sims
Statistics Consulting Laboratory, Bio5, University of Arizona, Tucson, Arizona, USA.
Shripad
S
Sinari
Statistics Consulting Laboratory, Bio5, University of Arizona, Tucson, Arizona, USA.
Dean
D
Billheimer
Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Elias K
EK
Haddad
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.|National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
Kristy O
KO
Murray
Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Arizona, USA.
Anne M
AM
Wertheimer
Department of Immunobiology, University of Arizona College of Medicine, Tucson, Arizona, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Arizona, USA.|Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA.
Janko
0000-0001-5830-5323
J
Nikolich-Žugich
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D000068884:Immunosenescence; D008213:Lymphocyte Activation; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D059467:Transcriptome; D014777:Virus Diseases / Q000276:immunology*; D055815:Young Adult