Skip to main content

Functional Analysis of Alloreactive Helper T Cells Involved in the Induction of Cytolytic T Cell Responses In Vitro

  • Chapter
Immunomodulation

Abstract

When T-responder cells are sensitized in vitro to foreign antigen presented on syngeneic cells or towards allogeneic stimulator cells, a proliferative response is initiated in which antigen specific cytotoxic T lymphocytes (CTL) are generated. The induction of CTL, however, requires the collaboration between functionally distinct T cell subpopulations1–5 and accessory cells from the macrophage lineage, including dendritic cells. The experimental data accumulated so far reveal a cascade of T-T cell interactions and distinct functions of their soluble products resulting in the “Interleukin concept”6 (Fig. 1). Upon receptor-antigen interaction, the “antigen-selected” clones of CTLp become sensitive to helper factors such as Interleukin-2 (IL-2).7 Il-2 binds to non-clonally distributed receptors on sensitized CTLp clones and thus induces CTL-P to proliferate. Their differentiation into cytolytic effector cells, however, requires another soluble helper factor, distinct from Il-2 and provisionally named cytotoxic T cell differentiation factor (CTDF).8,9 As with CTLp the activation of HTL-precursors (THTLp) also requires the appropriate antigen recognition by clonally distributed receptors. Upon binding to antigen the antigen selected HTL clones become sensitive to the inductive effect of Interleukin-1 (Il-1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. H. Wagner, Synergy during in vitro cytotoxic allograft responses. I. Evidence for cell interactions between thymocytes and peripheral T cells, J. Exp. Med. 138: 1379 (1973).

    Article  PubMed  CAS  Google Scholar 

  2. H. Cantor and E. Simpson, Regulation of the immune response by subclasses of T lymphocytes. I. Interactions between pre-killer T cells and regulatory T cells obtained from peripheral lymphoid tissues of mice, Eur. J. Immunol. 5: 330 (1975).

    Article  PubMed  CAS  Google Scholar 

  3. F.H. Bach, C. Grillot-Courvalin, O.J. Kuperman, H.W. Zollinger, C. Hayes, P.M. Sondel, B.J. Alter, and M.L. Bach, Antigenic requirements for triggering of cytotoxic T lymphocytes, Immunol Rev. 35: 76 (1977).

    Article  PubMed  CAS  Google Scholar 

  4. L.M. Pilarski, A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors, J. Exp. Med. 145: 709 (1977).

    Article  PubMed  CAS  Google Scholar 

  5. H. Wagner, M. Rollinghoff, K. Pfizenmaier, C. Hardt and G. Johnscher, T-T cell interactions during in vitro cytotoxic T lymphocyte responses. II. Helper factor from activated Lyt 1+ T cell is rate limiting (i) in T cell responses to non immunogenic alloantigen, (ii) in thymocyte responses to allogeneic stimulator cells, and (iii) recruits alloreactive or H-2 restricted CTL precursors from the Lyt 123+ T cell subset, J. Immunol. 124: 1058 (1980).

    PubMed  CAS  Google Scholar 

  6. H. Wagner, C. Hardt, H. Stockinger, K. Pfizenmaier, R. Bartlett and M. Rollinghoff, The impact of the thymus on the generation of immunocompetence and diversity of antigen-specific MHC-restricted cytotoxic T-lymphocyte precursors, Immunol. Rev. 58: 95 (1981).

    Article  PubMed  CAS  Google Scholar 

  7. H. Wagner, C. Hardt, K. Heeg, K. Pfizenmaier, W. Solbach, H. Stockinger and M. Rollinghoff, T-T cell interactions during cytotoxic T lymphocyte (CTL) responses: T cell derived helper factor (interleukin 2) as a probe to analyse CTL responsiveness and thymic mice maturation of CTL progenitors, Immunol. Rev. 51: 215 (1980).

    Article  PubMed  CAS  Google Scholar 

  8. H. Wagner, C. Hardt, M. Rouse, M. Rollinghoff, P. Scheurich and K. Pfizenmaier, Dissection of the proliferative and differentiative signals controlling murine cytotoxic T lymphocyte responses, J. Exp. Med, (in press, 1982).

    Google Scholar 

  9. D.H. Raulet and M.J. Bevan, A differentiation factor required for the expression of cytotoxic T cell function, Nature 296: 754 (1982).

    Article  PubMed  CAS  Google Scholar 

  10. E.L. Larsson, Functional heterogeneity of helper T cells: two distinct helper T cells are required for the production of T cell growth factor, J. Immunol, (in press, 1982).

    Google Scholar 

  11. J. Shaw, V. Monticone, G. Mills and V. Paetkau, Effects of co-stimulator on immune responses in vitro, J. Immunol. 120: 1974 (1978).

    PubMed  CAS  Google Scholar 

  12. H. Cantor and E.A. Boyse, Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclases of Ly+ cells in the generation of killer activity, J. Exp. Med. 141: 1390 (1975).

    Article  PubMed  CAS  Google Scholar 

  13. H. Cantor and E.A. Boyse, Regulation of cellular and humoral immune responses by T cell subclasses, Cold Spring Harbor Symp. Quant. Biol. 41: 23 (1976).

    Article  Google Scholar 

  14. M. Mage, B. Mathieson, S. Sharrow, L. McHugh, U. Hammerling, D. Kanellopoulos-Langevin, D. Brideau Jr. and C.A. Thomas III. Preparative nonlytic separation of Lyt- 2+ and Lyt-2– T lymphocytes, functional analyses of the separated cells and demonstration of synergy in graft-vs-host reaction of Lyt-2+ and Lyt-2– cells, Eur. J. Immunol. 11: 228 (1981).

    Article  PubMed  CAS  Google Scholar 

  15. P.E. Baker, S. Gillis, M.S. Ferm and K.A. Smith, The effect of T cell growth factor on the generation of cytolytic T cells, J. Immunol. 121: 2168 (1978).

    PubMed  CAS  Google Scholar 

  16. J.J. Farrar, Ph. L. Simon, W.J. Koopman and J. Fuller-Bonar, Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell-mediated immune responses, J. Immunol. 1353 (1978).

    Google Scholar 

  17. H. Wagner and M. Rollinghoff, T-T cell interactions during in vitro cytotoxic allograft responses. I. Soluble products from activated Ly 1+ T cells trigger autonomously antigen primed Ly 23+ T cells to cell proliferation and cytolytic activity, J. Exp. Med. 148: 1523 (1978).

    Article  PubMed  CAS  Google Scholar 

  18. M. Okada, G.R. Klimpel, R.C. Kuppers and C.S. Henney, The differentiation of cytotoxic T-cells in vitro. I. Amplifying factor(s) in the primary response is Lyt 1+ cell dependent, J. Immunol. 122: 2527 (1979).

    PubMed  CAS  Google Scholar 

  19. K. Pfizenmaier, R. Delzeit, M. Rollinhoff and H. Wagner, T-T cell interactions during in vitro cytotoxic T-lymphocyte responses. III. Antigen-specific T helper cells release non-specific mediator(s) able to help induction of H-2 restricted cytotoxic T lymphocyte responses across cell-impermeable membranes, Eur. J. Immunol. 10: 577 (1980).

    Article  PubMed  CAS  Google Scholar 

  20. H. Wagner, M. Rollinghoff, C. Hardt, and G.T. Johnscher, T-T cell interactions during in vitro cytotoxic T lymphocyte (CTL) responses, J. Immunol. 124: 1058 (1980).

    PubMed  CAS  Google Scholar 

  21. I. Lefkovits and H. Waldman, Limiting dilution analysis of cells in the immune system, Cambridge University Press, Cambridge, U.K. (1979).

    Google Scholar 

  22. M. Okada and C.S. Henney, The differentiation of cytotoxic T cells in vitro. II. Amplifying factor(s) produced in primary mixed lymphocyte cultures against K/D stimuli require the presence of Lyt 2+ cells but not Lyt 1+ cells, J. Immunol. 125: 300 (1980).

    PubMed  CAS  Google Scholar 

  23. H.R. MacDonald, J.-C. Cerottini, J.-E. Ryser, J.L. Maryanski, C. Taswell, M.B. Widmer and K.T. Brunner, Quantitation and cloning of cytolytic T lymphocytes and their precursors, Immunol. Rev. 51: 93 (1980).

    Article  PubMed  CAS  Google Scholar 

  24. C.T. Lutz, A.L. Glasebrook and F.W. Fitch, Enumeration of allo-reactive helper T lymphocytes which cooperate with cytolytic T lymphocytes. Eur. J. Immunol. 11: 726 (1981).

    Article  PubMed  CAS  Google Scholar 

  25. C.A. Janeway Jr., E.A. Lerner, J.M. Jason and B. Jones, T lymphocytes responding to M1s-locus antigens are Lyt-1+, 2– and I-A restricted. Immunogenetics 10: 481 (1980).

    Article  Google Scholar 

  26. K. Molnar-Kimber and J. Sprent, Absence of H-2 restriction in primary and secondary mixed lymphocyte reactions to strong M1s determinants. J. Exp. Med. 151: 407 (1980).

    Article  PubMed  CAS  Google Scholar 

  27. C. Taswell, H.R. MacDonald and J.-Ch., Clonal analysis of cytolytic T lymphocyte specificity. I. Phenotypically distinct sets of clones as the cellular basis of cross-reactivity to alloantigens. J. Exp. Med. 151: 1372 (1980).

    Article  PubMed  CAS  Google Scholar 

  28. C.A. Janeway Jr., E.A. Lerner, P.J. Conrad and B. Jones, The precision of self and non-self major histocompatibility complex encoded antigen recognition by cloned T cells. Behring Inst. Mitt. 70: 200 (1982).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1984 Plenum Press, New York

About this chapter

Cite this chapter

Krönke, M., Pfizenmaier, K., Wagner, H. (1984). Functional Analysis of Alloreactive Helper T Cells Involved in the Induction of Cytolytic T Cell Responses In Vitro . In: Fudenberg, H.H., Whitten, H.D., Ambrogi, F. (eds) Immunomodulation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9358-4_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-9358-4_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-9360-7

  • Online ISBN: 978-1-4615-9358-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics