Abstract
Requirements for the induction of human cytolytic T-lymphocyte (CTL) activity were studied in a monocyte-free T-cell activation system that uses immobilized anti-CD3 monoclonal antibodies (mAb) as a stimulus. Alloreactive CTL with specificity for HLA-A and -B locus antigens could be demonstrated within 2 days after the initiation of activation. CTL induction in purified T cells initiated by an optimal concentration of immobilized anti-CD3 mAb was not enhanced by the addition of monocytes or exogeneous cytokines, whereas addition of anti-CD25 mAb largely blocked the response. Upon suboptimal anti-CD3 mAb stimulation, addition of recombinant interleukin (rIL)-2, rIL-1 and rIL-4, but not recombinant interferon-gamma (IFN-gamma) or rIL-6, potentiated the development of CTL activity. Finally it was shown that immobilized anti-CD3 mAb induced significant levels of CTL activity in both purified CD4+ and CD8+ cells. This study indicates that the requirement for cytokines in the differentiation of CTL precursors depends on the strength of the activation signal delivered through the T-cell receptor.
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- Brakenhoff J. P., de Groot E. R., Evers R. F., Pannekoek H., Aarden L. A. Molecular cloning and expression of hybridoma growth factor in Escherichia coli. J Immunol. 1987 Dec 15;139(12):4116–4121. [PubMed] [Google Scholar]
- Cernetti C., Steinman R. M., Granelli-Piperno A. Identification of a 24-kDa cytokine that is required for development of cytolytic T lymphocytes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1605–1609. doi: 10.1073/pnas.85.5.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen L. K., Tourvieille B., Burns G. F., Bach F. H., Mathieu-Mahul D., Sasportes M., Bensussan A. Interferon: a cytotoxic T lymphocyte differentiation signal. Eur J Immunol. 1986 Jul;16(7):767–770. doi: 10.1002/eji.1830160709. [DOI] [PubMed] [Google Scholar]
- Chouaib S., Bensussan A., Termijtelen A. M., Andreeff M., Marchiol-Fournigault C., Fradelizi D., Dupont B. Allogeneic T cell activation triggering by MHC class I antigens. J Immunol. 1988 Jul 15;141(2):423–429. [PubMed] [Google Scholar]
- Collins J. M., Justement L. B., Stedman K. E., Zlotnik A., Campbell P. A. B cell stimulatory factor 1 induces lobster agglutinin 1-separated mouse thymocytes to express cytotoxic T lymphocyte activity. J Immunol. 1988 Jul 1;141(1):145–150. [PubMed] [Google Scholar]
- De Rie M. A., Kabel P., Sauerwein R. W., Van Lier R. A., Von dem Borne A. E., Melief C. J., Miedema F. Anti-HLA-class II monoclonal antibodies inhibit polyclonal B cell differentiation in vitro at the accessory cell level. Eur J Immunol. 1987 Jun;17(6):881–886. doi: 10.1002/eji.1830170623. [DOI] [PubMed] [Google Scholar]
- Dianzani U., Zarcone D., Pistoia V., Grossi C. E., Pileri A., Massaia M., Ferrarini M. CD8+CD11b+ peripheral blood T lymphocytes contain lymphokine-activated killer cell precursors. Eur J Immunol. 1989 Jun;19(6):1037–1044. doi: 10.1002/eji.1830190613. [DOI] [PubMed] [Google Scholar]
- Erard F., Corthesy P., Nabholz M., Lowenthal J. W., Zaech P., Plaetinck G., MacDonald H. R. Interleukin 2 is both necessary and sufficient for the growth and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. J Immunol. 1985 Mar;134(3):1644–1652. [PubMed] [Google Scholar]
- Farrar W. L., Johnson H. M., Farrar J. J. Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2. J Immunol. 1981 Mar;126(3):1120–1125. [PubMed] [Google Scholar]
- Geppert T. D., Lipsky P. E. Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. J Immunol. 1987 Mar 15;138(6):1660–1666. [PubMed] [Google Scholar]
- Gromo G., Geller R. L., Inverardi L., Bach F. H. Signal requirements in the step-wise functional maturation of cytotoxic T lymphocytes. Nature. 1987 Jun 4;327(6121):424–426. doi: 10.1038/327424a0. [DOI] [PubMed] [Google Scholar]
- Hardt C., Diamantstein T., Wagner H. Signal requirements for the in vitro differentiation of cytotoxic T lymphocytes (CTL): distinct soluble mediators promote preactivation of CTL-precursors, clonal growth and differentiation into cytotoxic effector cells. Eur J Immunol. 1985 May;15(5):472–478. doi: 10.1002/eji.1830150511. [DOI] [PubMed] [Google Scholar]
- Horii Y., Muraguchi A., Suematsu S., Matsuda T., Yoshizaki K., Hirano T., Kishimoto T. Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol. 1988 Sep 1;141(5):1529–1535. [PubMed] [Google Scholar]
- Horohov D. W., Stocks N. I., Siegel J. P. Limiting-dilution analysis of human CTL differentiation. Requirement for a lymphokine-mediated differentiation signal. Immunology. 1988 Sep;65(1):119–124. [PMC free article] [PubMed] [Google Scholar]
- Huizinga T. W., Kerst M., Nuyens J. H., Vlug A., von dem Borne A. E., Roos D., Tetteroo P. A. Binding characteristics of dimeric IgG subclass complexes to human neutrophils. J Immunol. 1989 Apr 1;142(7):2359–2364. [PubMed] [Google Scholar]
- Jung G., Honsik C. J., Reisfeld R. A., Müller-Eberhard H. J. Activation of human peripheral blood mononuclear cells by anti-T3: killing of tumor target cells coated with anti-target-anti-T3 conjugates. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4479–4483. doi: 10.1073/pnas.83.12.4479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jung G., Martin D. E., Müller-Eberhard H. J. Induction of cytotoxicity in human peripheral blood mononuclear cells by monoclonal antibody OKT3. J Immunol. 1987 Jul 15;139(2):639–644. [PubMed] [Google Scholar]
- Kabelitz D. Human cytotoxic lymphocytes. IV. Frequency and clonal specificity of CD8+CD16-(Leu2+Leu11-) and CD16+CD3-(Leu11+Leu4-) cytotoxic lymphocyte precursors activated by alloantigen or K562 stimulator cells. Cell Immunol. 1989 Jul;121(2):298–305. doi: 10.1016/0008-8749(89)90028-2. [DOI] [PubMed] [Google Scholar]
- Karagogeos D., Wortis H. H. Thymus grafts induce B cell development in nude, X-linked immune deficient mice. Eur J Immunol. 1987 Jan;17(1):141–144. doi: 10.1002/eji.1830170124. [DOI] [PubMed] [Google Scholar]
- Lanier L. L., Phillips J. H., Hackett J., Jr, Tutt M., Kumar V. Natural killer cells: definition of a cell type rather than a function. J Immunol. 1986 Nov 1;137(9):2735–2739. [PubMed] [Google Scholar]
- Leeuwenberg J. F., Spits H., Tax W. J., Capel P. J. Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies. J Immunol. 1985 Jun;134(6):3770–3775. [PubMed] [Google Scholar]
- Okada M., Kitahara M., Kishimoto S., Matsuda T., Hirano T., Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. 1988 Sep 1;141(5):1543–1549. [PubMed] [Google Scholar]
- Pfeifer J. D., McKenzie D. T., Swain S. L., Dutton R. W. B cell stimulatory factor 1 (interleukin 4) is sufficient for the proliferation and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. J Exp Med. 1987 Nov 1;166(5):1464–1470. doi: 10.1084/jem.166.5.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg A. S., Mizuochi T., Singer A. Evidence for involvement of dual-function T cells in rejection of MHC class I disparate skin grafts. Assessment of MHC class I alloantigens as in vivo helper determinants. J Exp Med. 1988 Jul 1;168(1):33–45. doi: 10.1084/jem.168.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott C. F., Jr, Lambert J. M., Bolender S., Blattler W. A. Resting human peripheral blood lymphocytes can be activated to cytolytic function by antibodies to CD3 in the absence of exogenous interleukin-2. Cell Immunol. 1988 Jul;114(2):370–384. doi: 10.1016/0008-8749(88)90329-2. [DOI] [PubMed] [Google Scholar]
- Shau H., Gray J. D., Golub S. H. Studies on cytotoxicity generated in human mixed lymphocyte culture. IV. Interleukin 2 alone or from mixed lymphocyte culture yields natural killer-like cytotoxic cells distinct from allospecific cytotoxic T lymphocytes. Cancer Immunol Immunother. 1988;27(3):255–260. doi: 10.1007/BF00205448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simon M. M., Hochgeschwender U., Brugger U., Landolfo S. Monoclonal antibodies to interferon-gamma inhibit interleukin 2-dependent induction of growth and maturation in lectin/antigen-reactive cytolytic T lymphocyte precursors. J Immunol. 1986 Apr 15;136(8):2755–2762. [PubMed] [Google Scholar]
- Staerz U. D., Bevan M. J. Cytotoxic T lymphocyte-mediated lysis via the Fc receptor of target cells. Eur J Immunol. 1985 Dec;15(12):1172–1177. doi: 10.1002/eji.1830151206. [DOI] [PubMed] [Google Scholar]
- Takai Y., Herrmann S. H., Greenstein J. L., Spitalny G. L., Burakoff S. J. Requirement for three distinct lymphokines for the induction of cytotoxic T lymphocytes from thymocytes. J Immunol. 1986 Dec 1;137(11):3494–3500. [PubMed] [Google Scholar]
- Takai Y., Wong G. G., Clark S. C., Burakoff S. J., Herrmann S. H. B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol. 1988 Jan 15;140(2):508–512. [PubMed] [Google Scholar]
- Van Lier R. A., Boot J. H., De Groot E. R., Aarden L. A. Induction of T cell proliferation with anti-CD3 switch-variant monoclonal antibodies: effects of heavy chain isotype in monocyte-dependent systems. Eur J Immunol. 1987 Nov;17(11):1599–1604. doi: 10.1002/eji.1830171112. [DOI] [PubMed] [Google Scholar]
- Van der Schoot C. E., Visser F. J., Tetteroo P. A., von dem Borne A. E. In-vitro differentiation of cells of patients with acute undifferentiated leukaemia. Br J Haematol. 1989 Mar;71(3):351–355. doi: 10.1111/j.1365-2141.1989.tb04291.x. [DOI] [PubMed] [Google Scholar]
- Vohr H. W., Hünig T. Induction of proliferative and cytotoxic responses in resting Lyt-2+ T cells with lectin and recombinant interleukin 2. Eur J Immunol. 1985 Apr;15(4):332–337. doi: 10.1002/eji.1830150405. [DOI] [PubMed] [Google Scholar]
- Widmer M. B., Acres R. B., Sassenfeld H. M., Grabstein K. H. Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor 1 (interleukin 4). J Exp Med. 1987 Nov 1;166(5):1447–1455. doi: 10.1084/jem.166.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Widmer M. B., Grabstein K. H. Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Nature. 1987 Apr 23;326(6115):795–798. doi: 10.1038/326795a0. [DOI] [PubMed] [Google Scholar]
- de Rie M. A., Schumacher T. N., van Schijndel G. M., van Lier R. A., Miedema F. Regulatory role of CD19 molecules in B-cell activation and differentiation. Cell Immunol. 1989 Feb;118(2):368–381. doi: 10.1016/0008-8749(89)90385-7. [DOI] [PubMed] [Google Scholar]
- van Lier R. A., Boot J. H., Verhoeven A. J., de Groot E. R., Brouwer M., Aarden L. A. Functional studies with anti-CD3 heavy chain isotype switch-variant monoclonal antibodies. Accessory cell-independent induction of interleukin 2 responsiveness in T cells by epsilon-anti-CD3. J Immunol. 1987 Nov 1;139(9):2873–2879. [PubMed] [Google Scholar]
- van Noesel C., Miedema F., Brouwer M., de Rie M. A., Aarden L. A., van Lier R. A. Regulatory properties of LFA-1 alpha and beta chains in human T-lymphocyte activation. Nature. 1988 Jun 30;333(6176):850–852. doi: 10.1038/333850a0. [DOI] [PubMed] [Google Scholar]