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. 1994 Mar 1;179(3):857–864. doi: 10.1084/jem.179.3.857

Interleukin 2 induces the expression of CD45RO and the memory phenotype by CD45RA+ peripheral blood lymphocytes

PMCID: PMC2191429  PMID: 8113679

Abstract

The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct "naive" and "memory" T cell subsets. While antigenic and mitogenic stimuli are known to initiate transition from the naive to memory state, little is known about the role of cytokines in this process. This report demonstrates that in vitro exposure of purified CD45RA+/CD45RO- peripheral blood lymphocytes (PBL) to interleukin 2 (IL-2) promotes their conversion to the CD45RA-/CD45RO+ phenotype. Conversion to CD45RO occurs for both the CD3+ and CD3-/CD56+ lymphocyte subsets, but occurs more rapidly, and at lower IL-2 concentrations, in the CD3-/CD56+ population. Expression of CD45RO was observed only in response to IL-2 and was not observed during long-term culture in IL-4, IL-6, or IL-7. We also examined the effect of IL-2 on the expression of adhesion molecules by T cells. The expression of CD2, CD11a, and CDw29 increased, and expression of Leu-8 (LAM-1) decreased, on cultured CD45RA+/CD45RO- cells after they converted to expression of CD45RO. In contrast, lymphocytes that remained CD45RA+/CD45RO- after 10 d in culture exhibited no change from their baseline adhesion molecule profile. Finally, to test the role of endogenous IL-2 during T cell activation we stimulated CD45RA+/CD45RO- PBL with immobilized anti-CD3 in the presence of neutralizing anti-IL-2 antibody and/or cyclosporin A. Both agents significantly reduced the expression of CD45RO and the effect of cyclosporin A was reversed by exogenous IL-2. We conclude that IL-2 promotes CD45RA+ cells to express the memory phenotype and is a mediator of CD45RO expression after stimulation of the T cell receptor/CD3 complex.

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Selected References

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  1. Akbar A. N., Salmon M., Janossy G. The synergy between naive and memory T cells during activation. Immunol Today. 1991 Jun;12(6):184–188. doi: 10.1016/0167-5699(91)90050-4. [DOI] [PubMed] [Google Scholar]
  2. Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
  3. Beverley P. C. Functional analysis of human T cell subsets defined by CD45 isoform expression. Semin Immunol. 1992 Feb;4(1):35–41. [PubMed] [Google Scholar]
  4. Braakman E., Sturm E., Vijverberg K., van Krimpen B. A., Gratama J. W., Bolhuis R. L. Expression of CD45 isoforms by fresh and activated human gamma delta T lymphocytes and natural killer cells. Int Immunol. 1991 Jul;3(7):691–697. doi: 10.1093/intimm/3.7.691. [DOI] [PubMed] [Google Scholar]
  5. Brod S. A., Rudd C. E., Purvee M., Hafler D. A. Lymphokine regulation of CD45R expression on human T cell clones. J Exp Med. 1989 Dec 1;170(6):2147–2152. doi: 10.1084/jem.170.6.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bukowski R. M., Sharfman W., Murthy S., Rayman P., Tubbs R., Alexander J., Budd G. T., Sergi J. S., Bauer L., Gibson V. Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. Cancer Res. 1991 Aug 15;51(16):4199–4205. [PubMed] [Google Scholar]
  7. Clement L. T. Isoforms of the CD45 common leukocyte antigen family: markers for human T-cell differentiation. J Clin Immunol. 1992 Jan;12(1):1–10. doi: 10.1007/BF00918266. [DOI] [PubMed] [Google Scholar]
  8. De Paoli P., Battistin S., Santini G. F. Age-related changes in human lymphocyte subsets: progressive reduction of the CD4 CD45R (suppressor inducer) population. Clin Immunol Immunopathol. 1988 Sep;48(3):290–296. doi: 10.1016/0090-1229(88)90022-0. [DOI] [PubMed] [Google Scholar]
  9. Dohlsten M., Hedlund G., Sjögren H. O., Carlsson R. Two subsets of human CD4+ T helper cells differing in kinetics and capacities to produce interleukin 2 and interferon-gamma can be defined by the Leu-18 and UCHL1 monoclonal antibodies. Eur J Immunol. 1988 Aug;18(8):1173–1178. doi: 10.1002/eji.1830180805. [DOI] [PubMed] [Google Scholar]
  10. Gergely P., Aszalos A. Effect of cyclosporin A on the anti-CD3 antibody- and concanavalin A-induced activation and membrane potential of human T lymphocytes. Immunopharmacology. 1990 Nov-Dec;20(3):191–199. doi: 10.1016/0162-3109(90)90034-c. [DOI] [PubMed] [Google Scholar]
  11. Harvey J., Jones D. B., Wright D. H. Leucocyte common antigen expression on T cells in normal and inflamed human gut. Immunology. 1989 Sep;68(1):13–17. [PMC free article] [PubMed] [Google Scholar]
  12. Kanner S. B., Deans J. P., Ledbetter J. A. Regulation of CD3-induced phospholipase C-gamma 1 (PLC gamma 1) tyrosine phosphorylation by CD4 and CD45 receptors. Immunology. 1992 Mar;75(3):441–447. [PMC free article] [PubMed] [Google Scholar]
  13. Kristensson K., Borrebaeck C. A., Carlsson R. Human CD4+ T cells expressing CD45RA acquire the lymphokine gene expression of CD45RO+ T-helper cells after activation in vitro. Immunology. 1992 May;76(1):103–109. [PMC free article] [PubMed] [Google Scholar]
  14. Ledbetter J. A., Rose L. M., Spooner C. E., Beatty P. G., Martin P. J., Clark E. A. Antibodies to common leukocyte antigen p220 influence human T cell proliferation by modifying IL 2 receptor expression. J Immunol. 1985 Sep;135(3):1819–1825. [PubMed] [Google Scholar]
  15. Lin J., Brown V. K., Justement L. B. Regulation of basal tyrosine phosphorylation of the B cell antigen receptor complex by the protein tyrosine phosphatase, CD45. J Immunol. 1992 Nov 15;149(10):3182–3190. [PubMed] [Google Scholar]
  16. Mackay C. R. T-cell memory: the connection between function, phenotype and migration pathways. Immunol Today. 1991 Jun;12(6):189–192. doi: 10.1016/0167-5699(91)90051-T. [DOI] [PubMed] [Google Scholar]
  17. Manyonda I. T., Soltys A. J., Hay F. C. A critical evaluation of the magnetic cell sorter and its use in the positive and negative selection of CD45RO+ cells. J Immunol Methods. 1992 Apr 27;149(1):1–10. doi: 10.1016/s0022-1759(12)80042-1. [DOI] [PubMed] [Google Scholar]
  18. Marathias K. P., Preffer F. I., Pinto C., Kradin R. L. Most human pulmonary infiltrating lymphocytes display the surface immune phenotype and functional responses of sensitized T cells. Am J Respir Cell Mol Biol. 1991 Nov;5(5):470–476. doi: 10.1165/ajrcmb/5.5.470. [DOI] [PubMed] [Google Scholar]
  19. Martorell J., Vilella R., Borche L., Rojo I., Vives J. A second signal for T cell mitogenesis provided by monoclonal antibodies CD45 (T200). Eur J Immunol. 1987 Oct;17(10):1447–1451. doi: 10.1002/eji.1830171010. [DOI] [PubMed] [Google Scholar]
  20. Mittler R. S., Greenfield R. S., Schacter B. Z., Richard N. F., Hoffmann M. K. Antibodies to the common leukocyte antigen (T200) inhibit an early phase in the activation of resting human B cells. J Immunol. 1987 May 15;138(10):3159–3166. [PubMed] [Google Scholar]
  21. Nguyen Q. H., Moy R. L., Roth M. D., Yamamoto R., Tomono S., Dubinett S. M. Expression of CD45 isoforms in fresh and IL-2-cultured tumor-infiltrating lymphocytes from basal cell carcinoma. Cell Immunol. 1993 Feb;146(2):421–430. doi: 10.1006/cimm.1993.1038. [DOI] [PubMed] [Google Scholar]
  22. Plebanski M., Saunders M., Burtles S. S., Crowe S., Hooper D. C. Primary and secondary human in vitro T-cell responses to soluble antigens are mediated by subsets bearing different CD45 isoforms. Immunology. 1992 Jan;75(1):86–91. [PMC free article] [PubMed] [Google Scholar]
  23. Robertson M. J., Caligiuri M. A., Manley T. J., Levine H., Ritz J. Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis. J Immunol. 1990 Nov 15;145(10):3194–3201. [PubMed] [Google Scholar]
  24. Salmon M., Kitas G. D., Bacon P. A. Production of lymphokine mRNA by CD45R+ and CD45R- helper T cells from human peripheral blood and by human CD4+ T cell clones. J Immunol. 1989 Aug 1;143(3):907–912. [PubMed] [Google Scholar]
  25. Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
  26. Starling G. C., Davidson S. E., McKenzie J. L., Hart D. N. Inhibition of natural killer-cell mediated cytolysis with monoclonal antibodies to restricted and non-restricted epitopes of the leucocyte common antigen. Immunology. 1987 Jul;61(3):351–356. [PMC free article] [PubMed] [Google Scholar]
  27. Sterry W., Bruhn S., Künne N., Lichtenberg B., Weber-Matthiesen K., Brasch J., Mielke V. Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration. Br J Dermatol. 1990 Jul;123(1):59–64. doi: 10.1111/j.1365-2133.1990.tb01824.x. [DOI] [PubMed] [Google Scholar]
  28. Streuli M., Hall L. R., Saga Y., Schlossman S. F., Saito H. Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens. J Exp Med. 1987 Nov 1;166(5):1548–1566. doi: 10.1084/jem.166.5.1548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Terada N., Or R., Weinberg K., Domenico J., Lucas J. J., Gelfand E. W. Transcription of IL-2 and IL-4 genes is not inhibited by cyclosporin A in competent T cells. J Biol Chem. 1992 Oct 15;267(29):21207–21210. [PubMed] [Google Scholar]
  30. Thomas M. L. The leukocyte common antigen family. Annu Rev Immunol. 1989;7:339–369. doi: 10.1146/annurev.iy.07.040189.002011. [DOI] [PubMed] [Google Scholar]
  31. Tonks N. K., Diltz C. D., Fischer E. H. CD45, an integral membrane protein tyrosine phosphatase. Characterization of enzyme activity. J Biol Chem. 1990 Jun 25;265(18):10674–10680. [PubMed] [Google Scholar]
  32. Volarević S., Burns C. M., Sussman J. J., Ashwell J. D. Intimate association of Thy-1 and the T-cell antigen receptor with the CD45 tyrosine phosphatase. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7085–7089. doi: 10.1073/pnas.87.18.7085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wallace D. L., Beverley P. C. Phenotypic changes associated with activation of CD45RA+ and CD45RO+ T cells. Immunology. 1990 Mar;69(3):460–467. [PMC free article] [PubMed] [Google Scholar]
  34. Wasik M. A., Morimoto C. Differential effects of cytokines on proliferative response of human CD4+ T lymphocyte subsets stimulated via T cell receptor-CD3 complex. J Immunol. 1990 May 1;144(9):3334–3340. [PubMed] [Google Scholar]
  35. de Jong R., Brouwer M., Miedema F., van Lier R. A. Human CD8+ T lymphocytes can be divided into CD45RA+ and CD45RO+ cells with different requirements for activation and differentiation. J Immunol. 1991 Apr 1;146(7):2088–2094. [PubMed] [Google Scholar]

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