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. 1990 Oct;82(1):108–113. doi: 10.1111/j.1365-2249.1990.tb05412.x

Signal requirements for activation of leukaemic T cells from a chronic lymphocytic leukaemia (T-CLL).

M R Zocchi 1, A Poggi 1, S Heltai 1, A Villa 1, L Inverardi 1, A Vicari 1, M G Sabbadini 1, M Ferrarini 1
PMCID: PMC1535161  PMID: 1976463

Abstract

In order to define the signal requirements for leukaemic T cell activation, the proliferation and interleukin-2 (IL-2) production of peripheral lymphocytes from a patient with a HTLV-I-, CD4+, CD45RA+ CD45RO+ CD25- T-CLL were evaluated after the delivery of different stimuli. Unlike resting CD4+ normal T lymphocytes that can be activated only by a two-signal stimulation, T-CLL cells proliferated and released IL-2 in response to a pair of anti-CD2 monoclonal antibodies (MoAbs) or concanavalin A (Con A) in the absence of both accessory cells (AC) and phorbol myristate acetate (PMA). The two stimuli were also able to induce CD25 expression within 12-20 h on the majority of T-CLL cells. A response to anti-CD3 and anti-CD28 MoAbs was detected only in the presence of PMA, similar to that observed in normal resting T lymphocytes matched for phenotype. Both Con A- and CD2-induced proliferation were strongly inhibited by the addition of anti-CD25 MoAb. Furthermore, T-CLL lymphocytes acquired anti-tumour lytic activity after culture in the presence of PMA and ionomycin. We conclude that HTLV1- CD25- T-CLL can be characterized not only by morphological and phenotypical studies but also on the basis of signal requirements for cell activation.

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Selected References

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  1. Gmünder H., Lesslauer W. A 45-kDa human T-cell membrane glycoprotein functions in the regulation of cell proliferative responses. Eur J Biochem. 1984 Jul 2;142(1):153–160. doi: 10.1111/j.1432-1033.1984.tb08263.x. [DOI] [PubMed] [Google Scholar]
  2. Hara T., Fu S. M., Hansen J. A. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J Exp Med. 1985 Jun 1;161(6):1513–1524. doi: 10.1084/jem.161.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hünig T., Mitnacht R., Tiefenthaler G., Köhler C., Miyasaka M. T11TS, the cell surface molecule binding to the "erythrocyte receptor" of T lymphocytes: cellular distribution, purification to homogeneity and biochemical properties. Eur J Immunol. 1986 Dec;16(12):1615–1621. doi: 10.1002/eji.1830161223. [DOI] [PubMed] [Google Scholar]
  4. Ledbetter J. A., Martin P. J., Spooner C. E., Wofsy D., Tsu T. T., Beatty P. G., Gladstone P. Antibodies to Tp67 and Tp44 augment and sustain proliferative responses of activated T cells. J Immunol. 1985 Oct;135(4):2331–2336. [PubMed] [Google Scholar]
  5. Manger B., Weiss A., Weyand C., Goronzy J., Stobo J. D. T cell activation: differences in the signals required for IL 2 production by nonactivated and activated T cells. J Immunol. 1985 Dec;135(6):3669–3673. [PubMed] [Google Scholar]
  6. Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Schlossman S. F., Reinherz E. L. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Moretta A., Pantaleo G., Lopez-Botet M., Moretta L. Involvement of T44 molecules in an antigen-independent pathway of T cell activation. Analysis of the correlations to the T cell antigen-receptor complex. J Exp Med. 1985 Sep 1;162(3):823–838. doi: 10.1084/jem.162.3.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Moretta A., Pantaleo G., Moretta L., Cerottini J. C., Mingari M. C. Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J Exp Med. 1983 Feb 1;157(2):743–754. doi: 10.1084/jem.157.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Moretta A., Poggi A., Olive D., Bottino C., Fortis C., Pantaleo G., Moretta L. Selection and characterization of T-cell variants lacking molecules involved in T-cell activation (T3 T-cell receptor, T44, and T11): analysis of the functional relationship among different pathways of activation. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1654–1658. doi: 10.1073/pnas.84.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  12. Olive D., Ragueneau M., Cerdan C., Dubreuil P., Lopez M., Mawas C. Anti-CD2 (sheep red blood cell receptor) monoclonal antibodies and T cell activation. I. Pairs of anti-T11.1 and T11.2 (CD2 subgroups) are strongly mitogenic for T cells in presence of 12-O-tetradecanoylphorbol 13-acetate. Eur J Immunol. 1986 Sep;16(9):1063–1068. doi: 10.1002/eji.1830160906. [DOI] [PubMed] [Google Scholar]
  13. Pawelec G., Busch F., Reinhold U., Rehbein A., Balko I., Bühring H. J. Division of human helper T cells into two sets on the basis of the induction of anti-tumor cytotoxicity by phorbol ester and calcium ionophore. Eur J Immunol. 1988 Jul;18(7):1147–1150. doi: 10.1002/eji.1830180729. [DOI] [PubMed] [Google Scholar]
  14. Poggi A., Bottino C., Zocchi M. R., Pantaleo G., Ciccone E., Mingari C., Moretta L., Moretta A. CD3+ WT31- peripheral T lymphocytes lack T44 (CD28), a surface molecule involved in activation of T cells bearing the alpha/beta heterodimer. Eur J Immunol. 1987 Jul;17(7):1065–1068. doi: 10.1002/eji.1830170725. [DOI] [PubMed] [Google Scholar]
  15. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sanders M. E., Makgoba M. W., Shaw S. Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today. 1988 Jul-Aug;9(7-8):195–199. doi: 10.1016/0167-5699(88)91212-1. [DOI] [PubMed] [Google Scholar]
  17. Selvaraj P., Plunkett M. L., Dustin M., Sanders M. E., Shaw S., Springer T. A. The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3. 1987 Mar 26-Apr 1Nature. 326(6111):400–403. doi: 10.1038/326400a0. [DOI] [PubMed] [Google Scholar]
  18. Smith S. H., Brown M. H., Rowe D., Callard R. E., Beverley P. C. Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology. 1986 May;58(1):63–70. [PMC free article] [PubMed] [Google Scholar]
  19. Tiefenthaler G., Hünig T., Dustin M. L., Springer T. A., Meuer S. C. Purified lymphocyte function-associated antigen-3 and T11 target structure are active in CD2-mediated T cell stimulation. Eur J Immunol. 1987 Dec;17(12):1847–1850. doi: 10.1002/eji.1830171227. [DOI] [PubMed] [Google Scholar]
  20. Tsudo M., Uchiyama T., Umadome H., Wano Y., Hori T., Tamori S., Uchino H., Kita K., Chiba S., Mitsutani S. Expression of interleukin-2 receptor on T cell chronic lymphocytic leukemia cells and their response to interleukin-2. Blood. 1986 Feb;67(2):316–321. [PubMed] [Google Scholar]
  21. Uchiyama T., Hori T., Tsudo M., Wano Y., Umadome H., Tamori S., Yodoi J., Maeda M., Sawami H., Uchino H. Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells. J Clin Invest. 1985 Aug;76(2):446–453. doi: 10.1172/JCI111992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Uchiyama T., Kamio M., Kodaka T., Tamori S., Fukuhara S., Amakawa R., Uchino H., Araki K. Leukemic cells from some adult T-cell leukemia patients proliferate in response to interleukin-4. Blood. 1988 Oct;72(4):1182–1186. [PubMed] [Google Scholar]
  23. Umadome H., Uchiyama T., Onishi R., Hori T., Uchino H., Nesumi N. Leukemic cells from a chronic T-lymphocytic leukemia patient proliferated in response to both interleukin-2 and interleukin-4 without prior stimulation and produced interleukin-2 mRNA with stimulation. Blood. 1988 Oct;72(4):1177–1181. [PubMed] [Google Scholar]
  24. 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]
  25. Weiss A., Imboden J., Hardy K., Manger B., Terhorst C., Stobo J. The role of the T3/antigen receptor complex in T-cell activation. Annu Rev Immunol. 1986;4:593–619. doi: 10.1146/annurev.iy.04.040186.003113. [DOI] [PubMed] [Google Scholar]
  26. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yang S. Y., Rhee S., Welte K., Dupont B. Differential in vitro activation of CD8-CD4+ and CD4-CD8+ T lymphocytes by combinations of anti-CD2 and anti-CD3 antibodies. J Immunol. 1988 Apr 1;140(7):2115–2120. [PubMed] [Google Scholar]

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