Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1990 Apr;69(4):536–541.

CD4+ CD45R- suppressor-inducer T-cell clones: requirements for cellular interaction, proliferation and lymphokines for the induction of suppression in peripheral blood mononuclear cells.

G Pawelec 1
PMCID: PMC1385625  PMID: 1692302

Abstract

Regulation of the induction of suppressive activity in peripheral blood mononuclear cells (PBMC) by human major histocompatibility complex (MHC) class II+ CD4+ CD45R+ suppressor-inducer T-cell clones has been investigated. Previously, it was shown that in this system, cyclosporin A-sensitive precursors gave rise to allo-indifferent MHC-unrestricted CD4+ suppressive cells. Their induction could be blocked by monoclonal antibodies (mAb) to multilocus MHC class II gene products (TU 39) but not by mAb preferentially reacting with HLA-DR, -DQ or -DP molecules. This product, functionally defined, was termed 'DY'. It is shown here that induction of suppression by DY follows established activation pathways: (i) cell adhesion was required because CD11a (LFA-1) mAb blocked suppressor-induction; (ii) CD4 mAb also blocked, consistent with the involvement of class II products in suppressor-induction; (iii) cell proliferation was required because mAb to transferrin receptors, or irradiation, inhibited induction; and (iv) such proliferation appeared to be interleukin (IL)-2-dependent because it was blocked by mAb to IL-2 receptor, and enhanced by exogenous IL-2 but not IL-4. It was also enhanced by exogenous IL-1 and IL-6, but not by IL-3, tumour necrosis factor-alpha (TNF alpha) or interferon-gamma (IFN-gamma). It therefore seems that the requirements for activation of suppression by CD4+ DY+ T-cell clones in this in vitro model bear many similarities to those for CD4+ helper T cells, namely, mediation by MHC class II with CD4 involvement, dependency on LFA-1-influenced cell interactions, and reliance on clonal expansion caused by IL-2 and possibly amplified by IL-1 and/or IL-6.

Full text

PDF
536

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbud-Filho M., Kupiec-Weglinski J. W., Araujo J. L., Heidecke C. D., Tilney N. L., Strom T. B. Cyclosporine therapy of rat heart allograft recipients and release of interleukins (IL 1, IL 2, IL 3): a role for IL 3 in graft tolerance? J Immunol. 1984 Nov;133(5):2582–2586. [PubMed] [Google Scholar]
  2. Busch F. W., Wernet P., Meyer P., Schneider E. M., Pawelec G. Modulation of in vitro myelopoiesis by alloreactive T cell clones. Blut. 1986 May;52(5):305–315. doi: 10.1007/BF00320794. [DOI] [PubMed] [Google Scholar]
  3. Ceuppens J. L., Baroja M. L., Lorre K., Van Damme J., Billiau A. Human T cell activation with phytohemagglutinin. The function of IL-6 as an accessory signal. J Immunol. 1988 Dec 1;141(11):3868–3874. [PubMed] [Google Scholar]
  4. Deusch K., Moebius U., Meyer zum Büschenfelde K. H., Meuer S. C. T lymphocyte control of autoreactivity: analysis with human T cell clones and limiting dilution culture. Eur J Immunol. 1986 Nov;16(11):1433–1438. doi: 10.1002/eji.1830161119. [DOI] [PubMed] [Google Scholar]
  5. Helle M., Boeije L., Aarden L. A. Functional discrimination between interleukin 6 and interleukin 1. Eur J Immunol. 1988 Oct;18(10):1535–1540. doi: 10.1002/eji.1830181010. [DOI] [PubMed] [Google Scholar]
  6. Hutchinson I. V. Suppressor T cells in allogeneic models. Transplantation. 1986 May;41(5):547–555. doi: 10.1097/00007890-198605000-00001. [DOI] [PubMed] [Google Scholar]
  7. Kurnick J. T., Hayward A. R., Altevogt P. Helper and suppressor-inducer activity of human T cells and their cloned progeny maintained in long-term culture. J Immunol. 1981 Apr;126(4):1307–1311. [PubMed] [Google Scholar]
  8. Lamb J. R., Fledmann M. A human suppressor T cell clone which recognizes an autologous helper T cell clone. Nature. 1982 Dec 2;300(5891):456–458. doi: 10.1038/300456a0. [DOI] [PubMed] [Google Scholar]
  9. Lancaster F., Chui Y. L., Batchelor J. R. Anti-idiotypic T cells suppress rejection of renal allografts in rats. Nature. 1985 May 23;315(6017):336–337. doi: 10.1038/315336a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Meuer S. C., Cooper D. A., Hodgdon J. C., Hussey R. E., Morimoto C., Schlossman S. F., Reinherz E. L. Immunoregulatory human T lymphocytes triggered as a consequence of viral infection: clonal analysis of helper, suppressor inducer and suppressor effector cell populations. J Immunol. 1983 Sep;131(3):1167–1172. [PubMed] [Google Scholar]
  12. Mohagheghpour N., Damle N. K., Moonka D. K., Terrell C. P., Engleman E. G. A human alloreactive inducer T cell clone that selectively activates antigen-specific suppressor T cells. J Immunol. 1984 Jul;133(1):133–136. [PubMed] [Google Scholar]
  13. Numerof R. P., Aronson F. R., Mier J. W. IL-2 stimulates the production of IL-1 alpha and IL-1 beta by human peripheral blood mononuclear cells. J Immunol. 1988 Dec 15;141(12):4250–4257. [PubMed] [Google Scholar]
  14. Pawelec G. P., Hadam M. R., Schneider E. M., Wernet P. Clonally restricted natural killer-like cytotoxicity displayed by cloned human T cell lines. J Immunol. 1982 Nov;129(5):2271–2276. [PubMed] [Google Scholar]
  15. Pawelec G. P., Rehbein A., Schaudt K., Busch F. W. IL-4-responsive human helper T cell clones are resistant to growth inhibition by tumor necrosis factor-alpha. J Immunol. 1989 Aug 1;143(3):902–906. [PubMed] [Google Scholar]
  16. Pawelec G. Allogeneically primed T lymphocyte clones in the analysis of lymphocyte stimulatory determinants. Hum Immunol. 1983 Dec;8(4):239–247. doi: 10.1016/0198-8859(83)90050-2. [DOI] [PubMed] [Google Scholar]
  17. Pawelec G., Balko I., Rehbein A. Cyclosporin A blocks the generation of alloindifferent but not of allospecific suppressive cells. Immunol Lett. 1988 Aug;18(4):293–296. doi: 10.1016/0165-2478(88)90177-0. [DOI] [PubMed] [Google Scholar]
  18. Pawelec G., Balko I., Reusch U., Rehbein A. Regulation of allospecific suppressive cell generation in vitro. Immunol Lett. 1988 Oct;19(2):121–126. doi: 10.1016/0165-2478(88)90130-7. [DOI] [PubMed] [Google Scholar]
  19. Pawelec G., Brocker T., Busch F. W., Bühring H. J., Fernandez N., Schneider E. M., Wernet P. "Tolerization" of human T-helper cell clones by chronic exposure to alloantigen: culture conditions dictate autocrine proliferative status but not acquisition of cytotoxic potential and suppressor-induction capacity. J Mol Cell Immunol. 1988;4(1):21–34. [PubMed] [Google Scholar]
  20. Pawelec G., Rehbein A., Müller C., Sonneborn H. H., Wernet P. Human T lymphocytes grown in T-cell growth factor: functional attributes in MLC, CML, PLT and allogeneic suppression. Immunology. 1981 Apr;42(4):529–540. [PMC free article] [PubMed] [Google Scholar]
  21. Pawelec G., Schneider E. M., Rehbein A., Balko I., Wernet P. Dissection of suppressor cell generation in vitro. Hum Immunol. 1986 Nov;17(3):343–354. doi: 10.1016/0198-8859(86)90285-5. [DOI] [PubMed] [Google Scholar]
  22. Pawelec G., Schneider E. M., Wernet P. Acquisition of suppressive activity and natural killer-like cytotoxicity by human alloproliferative "helper" T cell clones. J Immunol. 1986 Jan;136(2):402–411. [PubMed] [Google Scholar]
  23. Pawelec G., Schneider E. M., Wernet P. Cloned human T lymphocytes with lymphostimulatory capacity preferentially activate suppressor cells. Eur J Immunol. 1984 Apr;14(4):335–340. doi: 10.1002/eji.1830140411. [DOI] [PubMed] [Google Scholar]
  24. Quigley R. L., Wood K. J., Morris P. J. Mediation of antigen-induced suppression of renal allograft rejection by a CD4 (W3/25+) T cell. Transplantation. 1989 Apr;47(4):684–688. doi: 10.1097/00007890-198904000-00022. [DOI] [PubMed] [Google Scholar]
  25. Rosen-Bronson S., Eckels D. D. Longevity of human allospecific TLCs: mycoplasma infection as a cause of in vitro "suppression" of MLC. Hum Immunol. 1985 Dec;14(4):365–377. doi: 10.1016/0198-8859(85)90243-5. [DOI] [PubMed] [Google Scholar]
  26. Santoli D., Radka S. F., Igarashi M., Kreider B. L., Ferrone S. Autologous B lymphoblastoid cell lines and long-term cultured T cells as stimulators in the mixed lymphocyte reaction: analysis of the role of HLA class II antigens as stimulatory molecules. J Immunol. 1986 Jul 15;137(2):400–407. [PubMed] [Google Scholar]
  27. Scheurich P., Thoma B., Ucer U., Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987 Mar 15;138(6):1786–1790. [PubMed] [Google Scholar]
  28. Schneider E. M., Pawelec G., Shi L. R., Bühring H. J., Wernet P. Generation of CD4-positive suppressor T cells from mixed lymphocyte cultures in the presence of interleukin 2 receptor antibody TU69. An in vitro model for transplantation tolerance induction. Transplantation. 1987 Aug;44(2):295–302. doi: 10.1097/00007890-198708000-00023. [DOI] [PubMed] [Google Scholar]
  29. Schwab R., Crow M. K., Russo C., Weksler M. E. Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol. 1985 Sep;135(3):1714–1718. [PubMed] [Google Scholar]
  30. Spits H., Keizer G., Borst J., Terhorst C., Hekman A., de Vries J. E. Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines. Hybridoma. 1983;2(4):423–437. doi: 10.1089/hyb.1983.2.423. [DOI] [PubMed] [Google Scholar]
  31. Spits H., Yssel H., Takebe Y., Arai N., Yokota T., Lee F., Arai K., Banchereau J., de Vries J. E. Recombinant interleukin 4 promotes the growth of human T cells. J Immunol. 1987 Aug 15;139(4):1142–1147. [PubMed] [Google Scholar]
  32. Uchańska-Ziegler B., Wernet P., Liangru S., Ziegler A. Do monoclonal antibodies Tü15 and Tü67 detect heterogeneity of human transferrin receptor molecules? FEBS Lett. 1984 Oct 1;175(2):279–283. doi: 10.1016/0014-5793(84)80751-6. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES