Compensatory effect of TNFalpha on low natural killer activity in the elderly

• Autorzy: Mysliwska J. , Bryl E. , Trzonkowski P. , Mysliwski A.
• Języki publikacji: EN

Abstrakty

EN

Regulatory effect of CD25, an activation antigen the alpha subunit of interleukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was studied in fifty elderly (57-70 years old) and fifty young people (19-35 years old). Cytotoxic NK activity was assessed by 51Cr release assay, the levels of interleukin 2 (IL2) and tumour necrosis factors alpha (TNFalpha) were measured using bioassays and expression of CD16 and CD25 proteins by flow cytometry. Low NK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNFalpha during NK reaction. Inhibition of TNFalpha activity by anti-TNF monoclonal antibody suppressed exclusively NK activity of low NK responders. Moreover, stimulation in vitro of blood mononuclear cells, with TNFalpha induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its increased expression on NK cells of low NK responders would enable them to bind even low amounts of the endogenous IL2 available in this group of the elderly. Thus, an overproduction of TNFalpha seems to be a mechanism compensating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction.

Słowa kluczowe

EN

interleukin 2; antigen; health status; killer activity; tumour necrosis factor-alpha; natural killer; aging; immune response

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 2
• Opis fizyczny: p.301-311,fig.

Twórcy

autor

Mysliwska J.

• Medical University of Gdansk, Gdansk, Poland

autor

Bryl E.

autor

Trzonkowski P.

autor

Mysliwski A.

Bibliografia

• 1. Amadori, A., Zanovello, P., Cozzi, E., Ciminale, V., Borghesan, F., Fagiolo, U. & Crepaldi, G. (1988) Study of some elderly immunological parameters in aging humans. Gerontology 34, 277-283.
• 2. Gardner, I.D. (1980) The effect of ageing on susceptibility to infection. Rev. Infect. Dis. 2, 801-810.
• 3. Caruso, C., Candore, G., Cigna, D., DiLorenzo, G., Sireci, G., Dieli, F. & Salerno, A. (1996) Cytokine production pathway in the elderly. Immunol. Res. 15, 84-90.
• 4. Froelich, C.J., Burkett, J.S., Guiffaut, S., Kingsland, R. & Brauner, D. (1988) Phytohemagglutinin induced proliferation by aged lymphocytes: Reduced expression of high affinity interleukin-2 receptors and interleukin-2 secretion. Life Sci. 45, 1583-1590.
• 5. Chopra, R.K., Holbrook, N.J., Powers, D.C., McCoy, M.T., Adler, W.H. & Nagel, J.E. (1989) Interleukin 2, interleukin 2 receptor and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans. Clin. Immunol. Immunophatol. 53, 297-308.
• 6. Whisler, R.L., Beiqig, L. & Chau, M. (1996) Age related decreases in IL2 production by human T cells are associated with impaired activation of nuclear transcriptional factors AP-1 and NF-AT. Cell. Immunol. 1, 185-195.
• 7. Trebilcock, G.U. & Ponnappan, U. (1996) Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging. Gerontology 42, 137-146.
• 8. Song, L., Kim, Y.H., Chopra, R.K., Proust, J.J., Nagel, J.E., Nordin, A.A. & Adler, W.H. (1993) Age-related effects in T cell activation and proliferation. Exp. Gerontol. 28, 313-321.
• 9. Shabtai, M., Avigad, I., Schachter, P., Czerniak, A., Judich, A. & Ayalon, A. (1993) Analysis of peripheral blood lymphocyte cell surface density of functional and activation associated markers in young and old hemodialysis patients. J. Urol. 150, 1369-1374.
• 10. Hara, H., Tanaka, T., Negoro, S., Deguchi, Y., Nishio, S., Saiki, O. & Kishimoto, S. (1988) Age-related changes of expression of IL2 receptor subunits and kinetics of IL2 internalization in T cells after mitogenic stimulation. Mech. Ageing Dev. 45, 167-175.
• 11. Ligthart, G.J., Corberand, J.X., Fournier, C., Galanaud, P., Hijmans, W., Kennes, B., Muller-Hermelink, H.G. & Steinmann, G. (1984) Admission criteria for immunogerontological studies in man: The Senieur Protocol. Mech. Ageing Dev. 28, 47-55.
• 12. Mysliwska, J., Bryl, E., Zorena, K., Balon, J., Foerster, J. & Mysliwski, A. (1997) Overactivity of tumor necrosis factor-alpha but not interleukin 6 is associated with low natural killer cytotoxic activity in the elderly. Gerontology 43, 158-167.
• 13. Mysliwska, J., Bryl, E., Foerster, J. & Mysliwski, A. (1998) Increased interleukin 6 and decreased interleukin 2 production during the ageing process are influenced by the health status. Mech. Ageing Dev. 100, 313-328.
• 14. Trinchieri, G., Matsumoto-Kobayashi, M., Clark, S.C., Seehra, J., London, L. & Perussia, B. (1984) Response of resting human peripheral blood natural killer cells to interleukin 2. J. Exp. Med. 160, 1147-1169.
• 15. Ostensen, M.E., Thiele, D.L. & Lipsky, P.E. (1989) Enhancement of human natural killer cell function by the combined effects of tumor necrosis factor alpha or interleukin-1 and interferon­alpha or interleukin-2. J. Biol. Resp. Modif. 8, 53-61.
• 16. Owen-Schaub, L.B., Gutterman, J.U. & Grimm, E.A. (1988) Synergy of tumor necrosis factor and interleukin 2 in the activation of human cytotoxic lymphocytes: Effect of tumor necrosis factor alpha and interleukin 2 in the generation of human lymphokine-activated killer cell cytotoxicity. Cancer Res. 48, 788-792.
• 17. Naume, B., Shalaby, R., Lesslauer, W. & Espevik, T. (1991) Involvement of the 55- and 75-kDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells. J. Immunol. 146, 3045-3048.
• 18. Fagiolo, U., Cossarizza, A., Scala, E., Fanales- Belasio, E., Ortolani, C., Cozzi, E., Monti, D., Franceschi, C. & Paganelli, R. (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur. J. Immunol. 23, 2375-2378.
• 19. Mysliwska, J., Bryl, E., Foerster, J. & Mysliwski, A. (1999) The upregulation of TNF production is not a generalised phenomenon in the elderly. Mech. Ageing Dev. 107, 1-14.
• 20. Mooradian, A.D., Reed, R.L. & Scuderi, P. (1991) Serum levels of tumor necrosis factor alpha, interleukin-1 alpha and beta in healthy elderly subjects. Age 14, 61-64.
• 21. Mason, A.T., McVicar, D.W., Smith, C.A., Young, H.A., Ware, C.F. & Ortaldo, J.R. (1995) Regulation of NK cells through the 80-kDa TNFR (CD120b). J. Leukoc. Biol. 58, 249-255.
• 22. Chong, A.S., Scuderi, P., Grimes, W.J. & Hersh, E.M. (1989) Tumor targets stimulate IL2 activated killer cells to produce interferon-gamma and tumor necrosis factor. J. Immunol. 142, 2133-2139.