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. 1985 Aug;55(4):677–684.

Immunological studies of ageing. X. Impaired T lymphocytes and normal monocyte response from elderly humans to the mitogenic antibodies OKT3 and Leu 4.

R Schwab, P B Hausman, E Rinnooy-Kan, M E Weksler
PMCID: PMC1453768  PMID: 3874822

Abstract

Lymphocytes from old and young humans were cultured with PHA or the monoclonal antibodies OKT3 or Leu 4. The incorporation of [3H]TdR was significantly lower in cultures from old as compared to young donors, and the response of lymphocytes stimulated with OKT3 was the best discriminator of donor age. The mitogenic response of lymphocytes to these monoclonal antibodies requires monocytes. The response of T cells containing less than 5% adherent cells was diminished and the difference between old and young donors was not seen. The age-associated response was recovered when autologous or allogeneic monocytes were added to T cells. The age-associated response of T cells was the same, whether cultured with monocytes from young or old donors. Thus, monocytes from elderly subjects are not impaired with respect to their capacity to facilitate the proliferative response of T cells stimulated with monoclonal antibodies. Although lymphocytes from elderly donors were more sensitive to the inhibitory effect of prostaglandin E2, this did not account for the age-associated defect as indomethacin did not eliminate this defect. We conclude that the proliferative response of lymphocytes to OKT3 and Leu 4 is a more sensitive discriminator of lymphocyte donor age than is response to plant lectins, and that the age-associated defect in this response appears to reside within the T-cell population and not the monocyte population.

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Selected References

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  1. AboT, Tilden A. B., Balch C. M., Kumagai K., Troup G. M., Cooper M. D. Ethnic differences in the lymphocyte proliferative response induced by a murine IgG1 antibody, Leu-4, to the T3 molecule. J Exp Med. 1984 Jul 1;160(1):303–309. doi: 10.1084/jem.160.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Goodwin J. S. Changes in lymphocyte sensitivity to prostaglandin E, histamine, hydrocortisone, and X irradiation with age: studies in a healthy elderly population. Clin Immunol Immunopathol. 1982 Nov;25(2):243–251. doi: 10.1016/0090-1229(82)90187-8. [DOI] [PubMed] [Google Scholar]
  3. Gutowski J. K., Cohen S. Induction of DNA synthesis in isolated nuclei by cytoplasmic factors from spontaneously proliferating and mitogen-activated lymphoid cells. Cell Immunol. 1983 Feb 1;75(2):300–311. doi: 10.1016/0008-8749(83)90328-3. [DOI] [PubMed] [Google Scholar]
  4. Gutowski J. K., Innes J., Weksler M. E., Cohen S. Induction of DNA synthesis in isolated nuclei by cytoplasmic factors. II. Normal generation of cytoplasmic stimulatory factors by lymphocytes from aged humans with depressed proliferative responses. J Immunol. 1984 Feb;132(2):559–562. [PubMed] [Google Scholar]
  5. Kaneoka H., Perez-Rojas G., Sasasuki T., Benike C. J., Engleman E. G. Human T lymphocyte proliferation induced by a pan-T monoclonal antibody (anti-Leu 4): heterogeneity of response is a function of monocytes. J Immunol. 1983 Jul;131(1):158–164. [PubMed] [Google Scholar]
  6. Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
  7. Moody C. E., Innes J. B., Staiano-Coico L., Incefy G. S., Thaler H. T., Weksler M. E. Lymphocyte transformation induced by autologous cells. XI. The effect of age on the autologous mixed lymphocyte reaction. Immunology. 1981 Oct;44(2):431–438. [PMC free article] [PubMed] [Google Scholar]
  8. Reinherz E. L., Hussey R. E., Schlossman S. F. A monoclonal antibody blocking human T cell function. Eur J Immunol. 1980 Oct;10(10):758–762. doi: 10.1002/eji.1830101006. [DOI] [PubMed] [Google Scholar]
  9. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody with selective reactivity with functionally mature human thymocytes and all peripheral human T cells. J Immunol. 1979 Sep;123(3):1312–1317. [PubMed] [Google Scholar]
  10. Reinherz E. L., Meuer S., Fitzgerald K. A., Hussey R. E., Levine H., Schlossman S. F. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell. 1982 Oct;30(3):735–743. doi: 10.1016/0092-8674(82)90278-1. [DOI] [PubMed] [Google Scholar]
  11. Tax W. J., Willems H. W., Reekers P. P., Capel P. J., Koene R. A. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Nature. 1983 Aug 4;304(5925):445–447. doi: 10.1038/304445a0. [DOI] [PubMed] [Google Scholar]
  12. Van Wauwe J. P., De Mey J. R., Goossens J. G. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol. 1980 Jun;124(6):2708–2713. [PubMed] [Google Scholar]
  13. Van Wauwe J. P., Goossens J. G. The mitogenic activity of OKT3 and anti-Leu 4 monoclonal antibodies: a comparative study. Cell Immunol. 1983 Apr 1;77(1):23–29. doi: 10.1016/0008-8749(83)90003-5. [DOI] [PubMed] [Google Scholar]
  14. Van Wauwe J., Goossens J. Mitogenic actions of Orthoclone OKT3 on human peripheral blood lymphocytes: effects of monocytes and serum components. Int J Immunopharmacol. 1981;3(3):203–208. doi: 10.1016/0192-0561(81)90014-x. [DOI] [PubMed] [Google Scholar]
  15. Weksler M. E., Hütteroth T. H. Impaired lymphocyte function in aged humans. J Clin Invest. 1974 Jan;53(1):99–104. doi: 10.1172/JCI107565. [DOI] [PMC free article] [PubMed] [Google Scholar]

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