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. 1988 Nov;82(5):1722–1730. doi: 10.1172/JCI113786

Amplification of altered self-reactive cytolytic T lymphocyte responses by cloned, allospecific human Th cells.

S M Friedman 1, A Green 1, C Russo 1, D N Posnett 1, D Diffley 1, M K Crow 1
PMCID: PMC442743  PMID: 3263397

Abstract

The effect of a cloned allospecific human Th cell, termed 86, on the in vitro generation of altered self-reactive cytolytic T lymphocytes (CTL) was investigated. Utilizing the induction of hapten altered self-reactive CTL as a model for virus or tumor-specific cell-mediated immunity, we determined that the presence of small numbers of clone 86 cells markedly amplified the generation of hapten altered self-reactive CTL. The killer cells induced belong to the CD4-, CD8+ subset, are specific for the hapten-modified autologous stimulator cells present in culture, and are MHC class I restricted. The CTL induced under these culture conditions are readily expanded in the presence of IL-2 with maintenance of efficient and specific altered self-killing. Of interest, clone 86 cells preferentially enhance the growth of CD8+ T cells and selectively amplify altered self-cytolysis but not NK cell activity. Although in vitro clone 86 cells mediate help for CTL generation via the production of lymphokines (IL-4 but little IL-2), one can envision immunotherapeutic strategies for human disease that involve the adoptive transfer of Th cells functionally analogous to clone 86.

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Selected References

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

  1. Arthur R. P., Mason D. T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation. J Exp Med. 1986 Apr 1;163(4):774–786. doi: 10.1084/jem.163.4.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  3. Byrne J. A., Oldstone M. B. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol. 1984 Sep;51(3):682–686. doi: 10.1128/jvi.51.3.682-686.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cernetti C., Steinman R. M., Granelli-Piperno A. Identification of a 24-kDa cytokine that is required for development of cytolytic T lymphocytes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1605–1609. doi: 10.1073/pnas.85.5.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheever M. A., Greenberg P. D., Fefer A. Specific adoptive therapy of established leukemia with syngeneic lymphocytes sequentially immunized in vivo and in vitro and nonspecifically expanded by culture with Interleukin 2. J Immunol. 1981 Apr;126(4):1318–1322. [PubMed] [Google Scholar]
  6. Cheever M. A., Thompson D. B., Klarnet J. P., Greenberg P. D. Antigen-driven long term-cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy, and persist long-term as functional memory T cells. J Exp Med. 1986 May 1;163(5):1100–1112. doi: 10.1084/jem.163.5.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Defrance T., Aubry J. P., Rousset F., Vanbervliet B., Bonnefoy J. Y., Arai N., Takebe Y., Yokota T., Lee F., Arai K. Human recombinant interleukin 4 induces Fc epsilon receptors (CD23) on normal human B lymphocytes. J Exp Med. 1987 Jun 1;165(6):1459–1467. doi: 10.1084/jem.165.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernandez-Cruz E., Halliburton B., Feldman J. D. In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma. J Immunol. 1979 Oct;123(4):1772–1777. [PubMed] [Google Scholar]
  9. Friedman S. M., Hunter S. B., Irigoyen O. H., Kung P. C., Goldstein G., Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. II. Collaborative T-T interactions in the generation of TNP-altered-self-reactive cytotoxic T lymphocytes. J Immunol. 1981 May;126(5):1702–1705. [PubMed] [Google Scholar]
  10. Friedman S. M., Irigoyen O., Kuhns J., Chess L. Cell-mediated lympholysis of fluorescein isothiocyanate-conjugated autologous human cells: evidence for hapten-specific altered-self reactive human cytotoxic T lymphocytes. J Immunol. 1979 Jul;123(1):496–500. [PubMed] [Google Scholar]
  11. Friedman S. M., Neyhard N., Chess L. Cell-mediated lympholysis of trinitrophenyl-derivatized autologous human cells: in vitro triggering by nonspecific signals. J Immunol. 1978 Feb;120(2):630–637. [PubMed] [Google Scholar]
  12. Friedman S. M., Thompson G. S. Functionally restricted, allospecific, human helper T cell lines that amplify either B cell or cytolytic T cell responses. J Exp Med. 1983 May 1;157(5):1675–1680. doi: 10.1084/jem.157.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Friedman S. M., Thompson G. S., Principato M. A. Allospecific human T cell lines and clones which mediate HLA-DR restricted helper activity. J Immunol. 1982 Dec;129(6):2451–2457. [PubMed] [Google Scholar]
  14. Fyfe D. A., Finke J. H. Soluble helper factor(s) participates in the generation of cell mediated cytotoxicity directed against syngeneic tumor cells. J Immunol. 1979 Mar;122(3):1156–1161. [PubMed] [Google Scholar]
  15. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  16. Greenberg P. D., Cheever M. A., Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J Exp Med. 1981 Sep 1;154(3):952–963. doi: 10.1084/jem.154.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hui K., Grosveld F., Festenstein H. Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature. 1984 Oct 25;311(5988):750–752. doi: 10.1038/311750a0. [DOI] [PubMed] [Google Scholar]
  18. Janeway C. A., Jr, Conrad P. J., Lerner E. A., Babich J., Wettstein P., Murphy D. B. Monoclonal antibodies specific for Ia glycoproteins raised by immunization with activated T cells: possible role of T cellbound Ia antigens as targets of immunoregulatory T cells. J Immunol. 1984 Feb;132(2):662–667. [PubMed] [Google Scholar]
  19. Kupfer A., Swain S. L., Janeway C. A., Jr, Singer S. J. The specific direct interaction of helper T cells and antigen-presenting B cells. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6080–6083. doi: 10.1073/pnas.83.16.6080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kurt-Jones E. A., Hamberg S., Ohara J., Paul W. E., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J Exp Med. 1987 Dec 1;166(6):1774–1787. doi: 10.1084/jem.166.6.1774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lukacher A. E., Braciale V. L., Braciale T. J. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 1;160(3):814–826. doi: 10.1084/jem.160.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  23. Mulé J. J., Yang J. C., Afreniere R. L., Shu S. Y., Rosenberg S. A. Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2. J Immunol. 1987 Jul 1;139(1):285–294. [PubMed] [Google Scholar]
  24. Nagy Z., Elliott B. E., Nabholz M., Krammer P. H., Pernis B. Specific binding of alloantigens to T cells activated in the mixed lymphocyte reaction. J Exp Med. 1976 Mar 1;143(3):648–659. doi: 10.1084/jem.143.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. North R. J. Down-regulation of the antitumor immune response. Adv Cancer Res. 1985;45:1–43. doi: 10.1016/s0065-230x(08)60265-1. [DOI] [PubMed] [Google Scholar]
  26. Rosenberg S. A., Lotze M. T., Muul L. M., Chang A. E., Avis F. P., Leitman S., Linehan W. M., Robertson C. N., Lee R. E., Rubin J. T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987 Apr 9;316(15):889–897. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
  27. Russo C., Ng A. K., Pellegrino M. A., Ferrone S. The monoclonal antibody CR11-351 discriminates HLA-A2 variants identified by T cells. Immunogenetics. 1983;18(1):23–35. doi: 10.1007/BF00401353. [DOI] [PubMed] [Google Scholar]
  28. Shaw S., Nelson D. L., Shearer G. M. Human cytotoxic response in vitro to trinitrophenyl-modified autologous cells. I. T cell recognition of TNP in association with widely shared antigens. J Immunol. 1978 Jul;121(1):281–289. [PubMed] [Google Scholar]
  29. Shearer G. M., Rehn T. G., Schmitt-Verhulst A. M. Role of the murine major histocompatibility complex in the specificity of in vitro T-cell-mediated lympholysis against chemically-modified autologous lymphocytes. Transplant Rev. 1976;29:222–246. doi: 10.1111/j.1600-065x.1976.tb00203.x. [DOI] [PubMed] [Google Scholar]
  30. Takatsu K., Kikuchi Y., Takahashi T., Honjo T., Matsumoto M., Harada N., Yamaguchi N., Tominaga A. Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4234–4238. doi: 10.1073/pnas.84.12.4234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tanaka K., Hayashi H., Hamada C., Khoury G., Jay G. Expression of major histocompatibility complex class I antigens as a strategy for the potentiation of immune recognition of tumor cells. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8723–8727. doi: 10.1073/pnas.83.22.8723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weber J. S., Jay G., Tanaka K., Rosenberg S. A. Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection. J Exp Med. 1987 Dec 1;166(6):1716–1733. doi: 10.1084/jem.166.6.1716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Widmer M. B., Acres R. B., Sassenfeld H. M., Grabstein K. H. Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor 1 (interleukin 4). J Exp Med. 1987 Nov 1;166(5):1447–1455. doi: 10.1084/jem.166.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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