Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1980 May 1;151(5):1125–1138. doi: 10.1084/jem.151.5.1125

Multiple pathways of T-T interaction in the generation of cytotoxic T lymphocytes to alloantigens

PMCID: PMC2185861  PMID: 6966319

Abstract

The interaction of T helper (Th) cells with syngeneic and allogeneic cytotoxic T lymphocyte precursors (CTL.P) has been investigated. Unprimed and mixed lymphocyte culture-primed peripheral T cells were used as a source of Th. Thymocytes, which depend upon exogenous Th cells for activation, were used as a source of cytotoxic precursors. Data is presented that demonstrates that at least two pathways of T-T interaction can lead to the activation of cytotoxic lymphocytes. The first is an allogeneic effect, in which Th cells recognize and respond to alloantigens expressed on CTL.P. The second is the interaction of Th cells with syngeneic CTL.P, in which both cell types are thought to respond to alloantigens on stimulator cells. The latter interaction can be shown to be restricted by H-2-linked determinants when primed Th cells are used and allogeneic effects against thymocytes are minimized. Restricted interactions between unprimed Th cells and thymocyte CTL.P have never been observed. Mechanisms that may explain the difference between the interaction of unprimed and primed Th cells with CTL.P are discussed.

Full Text

The Full Text of this article is available as a PDF (792.0 KB).

Selected References

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

  1. Alter B. J., Bach F. H. Role of H-2 lymphocyte-defined and serologically-defined components in the generation of cytotoxic lymphocytes. J Exp Med. 1974 Nov 1;140(5):1410–1415. doi: 10.1084/jem.140.5.1410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altman A., Cohen I. R. Cell-free media of mixed lymphocyte cultures augmenting sensitization in vitro of mouse T lymphocytes against allogeneic fibroblasts. Eur J Immunol. 1976 Jul;5(7):437–444. doi: 10.1002/eji.1830050702. [DOI] [PubMed] [Google Scholar]
  3. Altman A., Cohen I. R. The nonspecific helper effect of mixed lymphocyte reactions on the induction of T cell-mediated immunity in vitro. Eur J Immunol. 1974 Aug;4(8):577–580. doi: 10.1002/eji.1830040811. [DOI] [PubMed] [Google Scholar]
  4. Baum L. L., Pilarski L. M. In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors. J Exp Med. 1978 Dec 1;148(6):1579–1591. doi: 10.1084/jem.148.6.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevan M. J., Langman R. E., Cohn M. H-2 antigen-specific cytotoxic T cells induced by concanavalin A: estimation of their relative frequency. Eur J Immunol. 1976 Mar;6(3):150–156. doi: 10.1002/eji.1830060303. [DOI] [PubMed] [Google Scholar]
  6. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cantor H., Boyse E. A. Regulation of cellular and humoral immune responses by T-cell subclasses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):23–32. doi: 10.1101/sqb.1977.041.01.006. [DOI] [PubMed] [Google Scholar]
  8. Corley R. B., Kindred B. In vivo responses of alloreactive lymphocytes stimulated in vitro. Helper-cell activity of MLR-primed lymphocytes. Scand J Immunol. 1977;6(9):923–932. doi: 10.1111/j.1365-3083.1977.tb00413.x. [DOI] [PubMed] [Google Scholar]
  9. Corley R. B., Kindred B. In vivo responses of alloreactive lymphocytes stimulated in vitro. Skin graft rejection mediated by MLR-Primed lymphocytes. Scand J Immunol. 1977;6(10):991–996. doi: 10.1111/j.1365-3083.1977.tb00334.x. [DOI] [PubMed] [Google Scholar]
  10. Corley R. B., Kindred B., Lefkovits I. Positive and negative allogeneic effects mediated by MLR-primed lymphocytes: quantitation by limiting dilution analysis. J Immunol. 1978 Sep;121(3):1082–1089. [PubMed] [Google Scholar]
  11. 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]
  12. Finke J. H., Orosz C. G., Battisto J. R. Splenic T-killer cells can be generated by allogeneic thymic cells in conjunction with assisting factor. Nature. 1977 May 26;267(5609):353–354. doi: 10.1038/267353a0. [DOI] [PubMed] [Google Scholar]
  13. Lafferty K. J., Misko I. S., Cooley M. A. Allogeneic stimulation modulates the in vitro response of T cells to transplantation antigen. Nature. 1974 May 17;249(454):275–276. doi: 10.1038/249275a0. [DOI] [PubMed] [Google Scholar]
  14. MacDonald H. R., Sordat B., Cerottini J. C., Brunner K. T. Generation of cytotoxic T lymphocytes in vitro. IV. Functional activation of memory cells in the absence of DNA synthesis. J Exp Med. 1975 Sep 1;142(3):622–636. doi: 10.1084/jem.142.3.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pilarski L. M. A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors. J Exp Med. 1977 Mar 1;145(3):709–725. doi: 10.1084/jem.145.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Plate J. M. Soluble factors substitute for T-T-cell collaboration in generation of T-killer lymphocytes. Nature. 1976 Mar 25;260(5549):329–331. doi: 10.1038/260329a0. [DOI] [PubMed] [Google Scholar]
  17. Röllinghoff M., Wagner H., Ovary Z. Induction of secondary cytotoxic T-lymphocytes in vitro does not require cell proliferation. Proc Soc Exp Biol Med. 1976 Feb;151(2):348–350. doi: 10.3181/00379727-151-39207. [DOI] [PubMed] [Google Scholar]
  18. Schreier M. H., Andersson J., Lernhardt W., Melchers F. Antigen-specific T-helper cells stimulate H-2-compatible and H-2-incompatible B-cell blasts polyclonally. J Exp Med. 1980 Jan 1;151(1):194–203. doi: 10.1084/jem.151.1.194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schreier M. H., Tees R. Clonal induction of helper T cells: conversion of specific signals into nonspecific signals. Int Arch Allergy Appl Immunol. 1980;61(2):227–237. doi: 10.1159/000232437. [DOI] [PubMed] [Google Scholar]
  20. Teh H. S., Phillips R. A., Miller R. G. Quantitative studies on the precursors of cytotoxic lymphocytes. II. Specificity of precursors responsive to alloantigens and to concanavalin A. J Immunol. 1977 Mar;118(3):1057–1062. [PubMed] [Google Scholar]
  21. Wagner H., Röllinghoff M., Schawaller R., Hardt C., Pfizenmaier K. T-cell-derived helper factor allows Lyt 123 thymocytes to differentiate into cytotoxic T lymphocytes. Nature. 1979 Aug 2;280(5721):405–406. doi: 10.1038/280405a0. [DOI] [PubMed] [Google Scholar]
  22. Wagner H., Röllinghoff M. T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity. J Exp Med. 1978 Dec 1;148(6):1523–1538. doi: 10.1084/jem.148.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wagner H. Synergy during in vitro cytotoxic allograft responses. I. Evidence for cell interaction between thymocytes and peripheral T cells. J Exp Med. 1973 Dec 1;138(6):1379–1397. doi: 10.1084/jem.138.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Streilein J. W., Klein J. The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help. J Exp Med. 1978 Mar 1;147(3):897–911. doi: 10.1084/jem.147.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. von Boehmer H., Haas W. Distinct Ir genes for helper and killer cells in the cytotoxic response to H-Y antigen. J Exp Med. 1979 Nov 1;150(5):1134–1142. doi: 10.1084/jem.150.5.1134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. von Boehmer H., Haas W., Jerne N. K. Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice. Proc Natl Acad Sci U S A. 1978 May;75(5):2439–2442. doi: 10.1073/pnas.75.5.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES