The Characterization of Varicella Zoster Virus-Specific T Cells in Skin and Blood during Aging.
Reactivation of the varicella zoster virus (VZV) increases during aging. Although the effects of VZV reactivation are observed in the skin (shingles), the number and functional capacity of cutaneous VZV-specific T cells have not been investigated. The numbers of circulating IFN-γ-secreting VZV-specific CD4(+) T cells are significantly decreased in old subjects. However, other measures of VZV-specific CD4(+) T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4(+) T cells with an major histocompatibility complex class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin-resident T cells. VZV-specific CD4(+) T cells were significantly increased in the skin compared with the blood in young and old subjects, and their function was similar in both age groups. In contrast, the number of Foxp3(+) regulatory T cells and expression of the inhibitory receptor programmed cell death -1 PD-1 on CD4(+) T cells were significantly increased in the skin of older humans. Therefore, VZV-specific CD4(+) T cells in the skin of older individuals are functionally competent. However, their activity may be restricted by multiple inhibitory influences in situ.
Division of Infection and Immunity, University College London, London, UK. Electronic address: m.vukmanovic-stejic@ucl.ac.uk.
Milica
M
Vukmanovic-Stejic
Division of Infection and Immunity, University College London, London, UK; Department of Dermatology, Royal Free Hospital, London, UK.
Daisy
D
Sandhu
Division of Infection and Immunity, University College London, London, UK.
Judith A
JA
Seidel
Division of Infection and Immunity, University College London, London, UK; Department of Dermatology, Royal Free Hospital, London, UK.
Neil
N
Patel
Division of Infection and Immunity, University College London, London, UK.
Toni O
TO
Sobande
Division of Infection and Immunity, University College London, London, UK; Department of Dermatology, Royal Free Hospital, London, UK.
Elaine
E
Agius
Division of Infection and Immunity, University College London, London, UK.
Sarah E
SE
Jackson
Laboratory for Investigative Dermatology, Rockefeller University, New York, USA.
Judilyn
J
Fuentes-Duculan
Laboratory for Investigative Dermatology, Rockefeller University, New York, USA.
Mayte
M
Suárez-Fariñas
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, UK.
Neil A
NA
Mabbott
St Johns Institute of Dermatology, Guys and St Thomas' Hospital, London, UK.
Katie E
KE
Lacy
MRC Human Immunology Unit, NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
Graham
G
Ogg
St Johns Institute of Dermatology, Guys and St Thomas' Hospital, London, UK.
Frank O
FO
Nestle
Laboratory for Investigative Dermatology, Rockefeller University, New York, USA.
James G
JG
Krueger
Department of Dermatology, Royal Free Hospital, London, UK.
Malcolm H A
MHA
Rustin
Division of Infection and Immunity, University College London, London, UK. Electronic address: a.akbar@ucl.ac.uk.
Arne N
AN
Akbar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000502:physiology; D001707:Biopsy, Needle; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006562:Herpes Zoster / Q000453:epidemiology / Q000503:physiopathology; D014645:Herpesvirus 3, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012867:Skin / Q000276:immunology / Q000473:pathology; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014775:Virus Activation / Q000276:immunology*; D055815:Young Adult