Abstract
A panel of monoclonal antibodies directed to different epitopes of porcine CD3 were employed to investigate stimulation requirements of porcine T lymphocytes. It was found that epitope specificity was an important property of the anti-CD3 antibodies that determined the requirements for T-cell proliferation. Thus, T-cell proliferation induced by triggering different CD3 epitopes showed three different requirements: (a) proliferation induced by the most insensitive epitope required both epitope ligation and some unknown additional signal(s); (b) proliferation induced by the most common epitopes only required epitope ligation, either by monocytes or by immobilization; (c) proliferation induced by the most sensitive epitope required neither epitope ligation nor participation of antigen-presenting cells (APC). These findings may help to explain the previous confusion over the requirements for T-cell activation through the CD3 pathway. Finally, the above conclusions apply only to alpha beta T cells, as porcine gamma delta T cells, either in bulk culture or isolated, did not proliferate in response to anti-CD3 stimulation. Therefore, the mechanism underlying gamma delta T-cell activation may be different from that of alpha beta T cells.
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- Alegre M. L., Peterson L. J., Xu D., Sattar H. A., Jeyarajah D. R., Kowalkowski K., Thistlethwaite J. R., Zivin R. A., Jolliffe L., Bluestone J. A. A non-activating "humanized" anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo. Transplantation. 1994 Jun 15;57(11):1537–1543. [PubMed] [Google Scholar]
- Arstila T. P., Toivanen P., Lassila O. Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response. Eur J Immunol. 1993 Aug;23(8):2034–2037. doi: 10.1002/eji.1830230848. [DOI] [PubMed] [Google Scholar]
- Banchereau J., de Paoli P., Vallé A., Garcia E., Rousset F. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science. 1991 Jan 4;251(4989):70–72. doi: 10.1126/science.1702555. [DOI] [PubMed] [Google Scholar]
- Bretscher P. The two-signal model of lymphocyte activation twenty-one years later. Immunol Today. 1992 Feb;13(2):74–76. doi: 10.1016/0167-5699(92)90138-W. [DOI] [PubMed] [Google Scholar]
- Carrel S., Salvi S., Rafti F., Favrot M., Rapin C., Sekaly R. P. Direct involvement of CD7 (gp40) in activation of TcR gamma/delta+ T cells. Eur J Immunol. 1991 May;21(5):1195–1200. doi: 10.1002/eji.1830210515. [DOI] [PubMed] [Google Scholar]
- Ceuppens J. L., Baroja M. L. Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase-bound OKT3. J Immunol. 1986 Sep 15;137(6):1816–1821. [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]
- Gimmi C. D., Freeman G. J., Gribben J. G., Gray G., Nadler L. M. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6586–6590. doi: 10.1073/pnas.90.14.6586. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green J. M., Noel P. J., Sperling A. I., Walunas T. L., Gray G. S., Bluestone J. A., Thompson C. B. Absence of B7-dependent responses in CD28-deficient mice. Immunity. 1994 Sep;1(6):501–508. doi: 10.1016/1074-7613(94)90092-2. [DOI] [PubMed] [Google Scholar]
- Green J. M., Thompson C. B. Modulation of T cell proliferative response by accessory cell interactions. Immunol Res. 1994;13(4):234–243. doi: 10.1007/BF02935615. [DOI] [PubMed] [Google Scholar]
- Hanby-Flarida M. D., Trask O. J., Yang T. J., Baldwin C. L. Modulation of WC1, a lineage-specific cell surface molecule of gamma/delta T cells augments cellular proliferation. Immunology. 1996 May;88(1):116–123. doi: 10.1046/j.1365-2567.1996.d01-649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harding F. A., McArthur J. G., Gross J. A., Raulet D. H., Allison J. P. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992 Apr 16;356(6370):607–609. doi: 10.1038/356607a0. [DOI] [PubMed] [Google Scholar]
- Holtrop S., Rijke-Schilder G. P., Koene R. A., Tax W. J. A polymorphic Fc receptor for mouse IgG2b on human B cells and monocytes. Immunology. 1991 Dec;74(4):613–620. [PMC free article] [PubMed] [Google Scholar]
- Jenkins M. K. The role of cell division in the induction of clonal anergy. Immunol Today. 1992 Feb;13(2):69–73. doi: 10.1016/0167-5699(92)90137-V. [DOI] [PubMed] [Google Scholar]
- Jonjić S., Koszinowski U. H. Monoclonal antibodies reactive with swine lymphocytes. I. Antibodies to membrane structures that define the cytolytic T lymphocyte subset in the swine. J Immunol. 1984 Aug;133(2):647–652. [PubMed] [Google Scholar]
- June C. H., Ledbetter J. A., Linsley P. S., Thompson C. B. Role of the CD28 receptor in T-cell activation. Immunol Today. 1990 Jun;11(6):211–216. doi: 10.1016/0167-5699(90)90085-n. [DOI] [PubMed] [Google Scholar]
- Kasahara Y., Chen C. H., Cooper M. D. Growth requirements for avian gamma delta T cells include exogenous cytokines, receptor ligation and in vivo priming. Eur J Immunol. 1993 Sep;23(9):2230–2236. doi: 10.1002/eji.1830230927. [DOI] [PubMed] [Google Scholar]
- Kawaguchi M., Eckels D. D. Differential activation through the TCR-CD3 complex affects the requirement for costimulation of human T cells. Hum Immunol. 1995 Jun;43(2):136–148. doi: 10.1016/0198-8859(94)00160-r. [DOI] [PubMed] [Google Scholar]
- Kawakami K., Yamamoto Y., Kakimoto K., Onoue K. Requirement for delivery of signals by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T cell proliferation. Effectiveness of IFN-gamma modulation of accessory cells for physical interaction with T cells. J Immunol. 1989 Mar 15;142(6):1818–1825. [PubMed] [Google Scholar]
- Klausner R. D., Samelson L. E. T cell antigen receptor activation pathways: the tyrosine kinase connection. Cell. 1991 Mar 8;64(5):875–878. doi: 10.1016/0092-8674(91)90310-u. [DOI] [PubMed] [Google Scholar]
- Krutmann J., Kirnbauer R., Köck A., Schwarz T., Schöpf E., May L. T., Sehgal P. B., Luger T. A. Cross-linking Fc receptors on monocytes triggers IL-6 production. Role in anti-CD3-induced T cell activation. J Immunol. 1990 Sep 1;145(5):1337–1342. [PubMed] [Google Scholar]
- Pescovitz M. D., Lunney J. K., Sachs D. H. Preparation and characterization of monoclonal antibodies reactive with porcine PBL. J Immunol. 1984 Jul;133(1):368–375. [PubMed] [Google Scholar]
- Rao P. E., Olini G., Kille J., Muchmore E., Talle M. A., Brake G., Rudnick S. A. OKT3E, an anti-CD3 antibody that does not elicit side effects or antiidiotype responses in chimpanzees. Transplantation. 1991 Oct;52(4):691–697. doi: 10.1097/00007890-199110000-00021. [DOI] [PubMed] [Google Scholar]
- Schlitt H. J., Kurrle R., Wonigeit K. T cell activation by monoclonal antibodies directed to different epitopes on the human T cell receptor/CD3 complex: evidence for two different modes of activation. Eur J Immunol. 1989 Sep;19(9):1649–1655. doi: 10.1002/eji.1830190920. [DOI] [PubMed] [Google Scholar]
- Schwinzer R., Franklin R. A., Domenico J., Renz H., Gelfand E. W. Monoclonal antibodies directed to different epitopes in the CD3-TCR complex induce different states of competence in resting human T cells. J Immunol. 1992 Mar 1;148(5):1322–1328. [PubMed] [Google Scholar]
- Tan P., Anasetti C., Hansen J. A., Melrose J., Brunvand M., Bradshaw J., Ledbetter J. A., Linsley P. S. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993 Jan 1;177(1):165–173. doi: 10.1084/jem.177.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tunnacliffe A., Olsson C., de la Hera A. The majority of human CD3 epitopes are conferred by the epsilon chain. Int Immunol. 1989;1(5):546–550. doi: 10.1093/intimm/1.5.546. [DOI] [PubMed] [Google Scholar]
- Verwilghen J., Baroja M. L., Van Vaeck F., Van Damme J., Ceuppens J. L. Differences in the stimulating capacity of immobilized anti-CD3 monoclonal antibodies: variable dependence on interleukin-1 as a helper signal for T-cell activation. Immunology. 1991 Feb;72(2):269–276. [PMC free article] [PubMed] [Google Scholar]
- Vine J. B., Geppert T. D., Lipsky P. E. Precursor frequency of human T4 cells responding to stimulation through the CD3 molecular complex: role of various cytokines in promoting growth and IL2 production. Cell Immunol. 1989 Dec;124(2):212–226. doi: 10.1016/0008-8749(89)90126-3. [DOI] [PubMed] [Google Scholar]
- Willems F., Andris F., Xu D., Abramowicz D., Wissing M., Goldman M., Leo O. The induction of human T cell unresponsiveness by soluble anti-CD3 mAb requires T cell activation. Int Immunol. 1995 Oct;7(10):1593–1598. doi: 10.1093/intimm/7.10.1593. [DOI] [PubMed] [Google Scholar]
- Williams M. E., Shea C. M., Lichtman A. H., Abbas A. K. Antigen receptor-mediated anergy in resting T lymphocytes and T cell clones. Correlation with lymphokine secretion patterns. J Immunol. 1992 Sep 15;149(6):1921–1926. [PubMed] [Google Scholar]
- Wu Y. J., Tian W. T., Snider R. M., Rittershaus C., Rogers P., LaManna L., Ip S. H. Signal transduction of gamma/delta T cell antigen receptor with a novel mitogenic anti-delta antibody. J Immunol. 1988 Sep 1;141(5):1476–1479. [PubMed] [Google Scholar]
- Yang H., Oura C. A., Kirkham P. A., Parkhouse R. M. Preparation of monoclonal anti-porcine CD3 antibodies and preliminary characterization of porcine T lymphocytes. Immunology. 1996 Aug;88(4):577–585. doi: 10.1046/j.1365-2567.1996.d01-682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang H., Parkhouse R. M. Phenotypic classification of porcine lymphocyte subpopulations in blood and lymphoid tissues. Immunology. 1996 Sep;89(1):76–83. doi: 10.1046/j.1365-2567.1996.d01-705.x. [DOI] [PMC free article] [PubMed] [Google Scholar]