Abstract
T cell hybridoma lines were constructed by fusion of DBA/2 alloantigen- activated T cell blasts with the AKR thymoma line BW5147. Certain of the hybridomas prepared in this manner secreted spontaneously into their culture supernates biologically active molecules that displayed B cell- and T cell-activating properties characteristic of allogeneic effect factor (AEF). Cell surface phenotype analysis documented that the hybridomas were, indeed, somatic cell hybrids between the two respective partner cells used for fusion. The B cell-activating properties of these hybridoma supernates was demonstrated by their capacity to stimulate T cell-depleted spleen cells to respond in vitro to T-dependent antigens. The T cell-activating properties of these hybridoma supernates was verified by their capacity to stimulate autonomous development of self-specific cytotoxic T lymphocytes and by their capacity to exert mitogenic effects on unprimed T cells. The biologically active molecules secreted by these hybridomas were, like conventional AEF, inhibitable by specific anti-Ia antibodies thus indicating the presence of Ia determinants on the relevant hybridoma products. Finally, these AEF-secreting hybridomas could be stimulated to proliferate and to secrete increased quantities of AEF when exposed to the specific alloantigen-bearing target cells to which the T cell blasts had been originally sensitized.
Full Text
The Full Text of this article is available as a PDF (906.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aguet M., Andersson L. C., Andersson R., Wight E., Binz H., Wigzell H. Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. II. An analysis of the effects measured at the cellular and serological levels. J Exp Med. 1978 Jan 1;147(1):50–61. doi: 10.1084/jem.147.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Altman A., Bechtold T. E., Cardenas J. M., Katz D. H. Biological effects of allogeneic effect factor on T lymphocytes: in vitro induction of cytotoxic T lymphocytes manifesting preferential lytic activity against H-2-identical tumor cells. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3477–3481. doi: 10.1073/pnas.76.7.3477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Altman A., Bechtold T. E., Katz D. H. Manipulation of cytotoxic T lymphocyte responses to syngeneic tumors. I. Hapten-reactive helper T lymphocytes augment tumor-specific CTL responses in vitro. J Immunol. 1979 Jun;122(6):2484–2490. [PubMed] [Google Scholar]
- Altman A., Cardenas J. M., Bechtold T. E., Katz D. H. The biologic effects of allogeneic factor on T lymphocytes. II. The specificity of AEF-induced cytotoxic T lymphocytes. J Immunol. 1980 Jan;124(1):114–120. [PubMed] [Google Scholar]
- Altman A., Cardenas J. M., Welsh R. M., Jr, Katz D. H. The biological effects of allogeneic effect factor (AEF) on T lymphocytes. III.--Interferon does not contribute to the biological activities displayed by AEF on both T and B lymphocytes. Ann Immunol (Paris) 1980 May-Jun;131C(3):335–347. [PubMed] [Google Scholar]
- Altman A., Katz D. H. The induction of autoreactive T lymphocytes by allogeneic effect factor (AEF): relevance to normal pathways of lymphocyte differentiation. Immunol Rev. 1980;51:3–34. doi: 10.1111/j.1600-065x.1980.tb00315.x. [DOI] [PubMed] [Google Scholar]
- Armerding D., Eshhar Z., Katz D. H. Activation of T and B lymphocytes in vitro. VI. Biochemical and physicochemical characterization of the allogeneic effect factor. J Immunol. 1977 Oct;119(4):1468–1474. [PubMed] [Google Scholar]
- Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes. J Exp Med. 1974 Jul 1;140(1):19–37. doi: 10.1084/jem.140.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armerding D., Kubo R. T., Grey H. M., Katz D. H. Activation of T and B lymphocytes in vitro: presence of beta2-microblobulin determinants on allogeneic effect factor. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4577–4581. doi: 10.1073/pnas.72.11.4577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armerding D., Sachs D. H., Katz D. H. Activation of T and B lymphocytes in vitro. III. Presence of Ia determinants on allogeneic effect factor. J Exp Med. 1974 Dec 1;140(6):1717–1722. doi: 10.1084/jem.140.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Click R. E., Benck L., Alter B. J. Immune responses in vitro. I. Culture conditions for antibody synthesis. Cell Immunol. 1972 Feb;3(2):264–276. doi: 10.1016/0008-8749(72)90165-7. [DOI] [PubMed] [Google Scholar]
- Delovitch T. L., Biggin J., Fung F. Y. In vitro analysis of allogeneic lymphocyte interaction. II. I-region control of the activity of a B-cell-derived H-2-restricted allogeneic effect factor and its receptor during B-cell activation. J Exp Med. 1978 Apr 1;147(4):1198–1212. doi: 10.1084/jem.147.4.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delovitch T. L., McDevitt H. O. In vitro analysis of allogeneic lymphocyte interaction. I. Characterization and cellular origin of an Ia-positive helper factor-allogeneic effect factor. J Exp Med. 1977 Oct 1;146(4):1019–1032. doi: 10.1084/jem.146.4.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eshhar Z., Armerding D., Waks T., Katz D. H. Activation of T and B lymphocytes in vitro. V. Cellular locus, metabolism and genetics of induction, and production of the allogeneic effect factor. J Immunol. 1977 Oct;119(4):1457–1467. [PubMed] [Google Scholar]
- Fridman W. H., Golstein P. Immunoglobulin-binding factor present on and produced by thymus-processed lymphocytes (T cells). Cell Immunol. 1974 Mar 30;11(1-3):442–455. doi: 10.1016/0008-8749(74)90042-2. [DOI] [PubMed] [Google Scholar]
- Gefter M. L., Margulies D. H., Scharff M. D. A simple method for polyethylene glycol-promoted hybridization of mouse myeloma cells. Somatic Cell Genet. 1977 Mar;3(2):231–236. doi: 10.1007/BF01551818. [DOI] [PubMed] [Google Scholar]
- Goldsby R. A., Osborne B. A., Simpson E., Herzenberg L. A. Hybrid cell lines with T-cell characteristics. Nature. 1977 Jun 23;267(5613):707–708. doi: 10.1038/267707a0. [DOI] [PubMed] [Google Scholar]
- Hewitt J., Liew F. Y. Antigen-specific suppressor factors produced by T cell hybridomas for delayed-type hypersensitivity. Eur J Immunol. 1979 Jul;9(7):572–575. doi: 10.1002/eji.1830090714. [DOI] [PubMed] [Google Scholar]
- Hämmerling G. J. T lymphocyte tissue culture lines produced by cell hybridization. Eur J Immunol. 1977 Oct;7(10):743–746. doi: 10.1002/eji.1830071018. [DOI] [PubMed] [Google Scholar]
- Katz D. H., Osborne D. P., Jr The allogeneic effect in inbred mice. II. Establishment of the cellular interactions required for enhancement of antibody production by the graft-versus-host reaction. J Exp Med. 1972 Sep 1;136(3):455–465. doi: 10.1084/jem.136.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kontiainen S., Simpson E., Bohrer E., Beverley P. C., Herzenberg L. A., Fitzpatrick W. C., Vogt P., Torano A., McKenzie I. F., Feldmann M. T-cell lines producing antigen-specific suppressor factor. Nature. 1978 Aug 3;274(5670):477–480. doi: 10.1038/274477a0. [DOI] [PubMed] [Google Scholar]
- Köhler G., Lefkovits I., Elliott B., Coutinho A. Derivation of hybrids between a thymoma line and spleen cells activated in a mixed leukocyte reaction. Eur J Immunol. 1977 Nov;7(11):758–761. doi: 10.1002/eji.1830071103. [DOI] [PubMed] [Google Scholar]
- Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
- Neauport-Sautes C., Rabourdin-Combe C., Fridman W. H. T-cell hybrids bear Fcgamma receptors and secrete suppressor immunoglobulin binding factor. Nature. 1979 Feb 22;277(5698):656–659. doi: 10.1038/277656a0. [DOI] [PubMed] [Google Scholar]
- Rabourdin-Combe C., Dorf M. E., Guimezanes A., Fridman W. H. T cell-produced immunoglobulin binding factor (IBF) bears determinants coded for by the I region of the major histocompatibility complex and lacks allogeneic restriction. Eur J Immunol. 1979 Mar;9(3):237–242. doi: 10.1002/eji.1830090313. [DOI] [PubMed] [Google Scholar]
- Schrader J. W., Arnold B., Clark-Lewis I. A con A-stimulated T-cell hybridoma releases factors affecting haematopoietic colony-forming cells and B-cell antibody responses. Nature. 1980 Jan 10;283(5743):197–199. doi: 10.1038/283197a0. [DOI] [PubMed] [Google Scholar]
- Skidmore B. J., Miller L. S. The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras. J Immunol Methods. 1978;24(3-4):337–343. doi: 10.1016/0022-1759(78)90136-9. [DOI] [PubMed] [Google Scholar]
- Taniguchi M., Miller J. F. Specific suppressive factors produced by hybridomas derived from the fusion of enriched suppressor T cells and a T lymphoma cell line. J Exp Med. 1978 Aug 1;148(2):373–382. doi: 10.1084/jem.148.2.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taniguchi M., Saito T., Tada T. Antigen-specific suppressive factor produced by a transplantable I-J bearing T-cell hybridoma. Nature. 1979 Apr 5;278(5704):555–558. doi: 10.1038/278555a0. [DOI] [PubMed] [Google Scholar]
- Taussig M. J., Corvalan J. R., Binns R. M., Holliman A. Production of an H--2-related suppressor factor by a hybrid T-cell line. Nature. 1979 Jan 25;277(5694):305–308. doi: 10.1038/277305a0. [DOI] [PubMed] [Google Scholar]
- Taussig M. J., Holliman A. Structure of an antigen-specific suppressor factor produced by a hybrid T-cell line. Nature. 1979 Jan 25;277(5694):308–310. doi: 10.1038/277308a0. [DOI] [PubMed] [Google Scholar]
- Watanabe T., Kimoto M., Maruyama S., Kishimoto T., Yamamura Y. Regulation of antibody response in different immunoglobulin classes. V. Establishment of T hybrid cell line secreting IgE class-specific suppressor factor. J Immunol. 1978 Nov;121(5):2113–2117. [PubMed] [Google Scholar]