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Blood, Vol. 92 No. 7 (October 1), 1998: pp. 2410-2420

Age-Related Decline of Perforin Expression in Human Cytotoxic T Lymphocytes and Natural Killer Cells

Daniel Rukavina, Gordana Laskarin, Gordana Rubesa, Natasa Strbo, Ivica Bedenicki, Darko Manestar, Mario Glavas, Stephen E. Christmas, and Eckhard R. Podack

From the Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka; the Department of Otorhinolaringology, Clinical Hospital Center, University of Rijeka, Rijeka, Croatia; the Clinical Hospital Center Pula, Pula, Croatia; the Department of Immunology, University of Liverpool, Liverpool, UK; and the Department of Microbiology and Immunology, University of Miami, Miami, FL.

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.


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