Age-related decline of perforin expression in human cytotoxic T lymphocytes and natural killer cells.
In this study a flow cytometric technique for detecting cytoplasmic perforin (P) has been used to quantify age-related changes in perforin expression in human peripheral blood lymphocytes (PBL). Proportions of P+ lymphocytes increased after birth, but declined rapidly after the age of 70 years. This was true for both T cells and CD16(+) and CD56(+) natural killer (NK) cells. Children showed in addition to high levels of perforin positive CD8(+) cells a much higher proportion of CD4(+)P+ cells than the other age groups. In elderly individuals there was also a highly significant reduction in mean levels of perforin per cell as compared with all other groups (P < .05 to .001). Adult women had consistently higher mean levels of perforin per cell than adult men for all P+ cell phenotypes. Functional tests clearly showed the deficiency in early spontaneous cytotoxic potential of PBL from elderly persons due to relative P deficiency, which can be corrected by stimulation of cytolytic cells with target cells and interleukin-2 (IL-2). The deficiency in cytolytic activity on the contact with target cells may have implications for antiviral and antitumor immunity in elderly persons.
Rukavina
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Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia. Daniel.Rukavina@mamed.medri.hr
Laskarin
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Rubesa
G
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Strbo
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N
Bedenicki
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I
Manestar
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Glavas
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M
Christmas
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Podack
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ER
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007121:Immunocompetence / Q000235:genetics; D007231:Infant, Newborn; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012727:Sex Characteristics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000378:metabolism*
D007519:Isoantigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin