Skip to main content
NCBI home page
Cytotechnology logoLink to Cytotechnology
. 2000 Oct;34(1-2):101–110. doi: 10.1023/A:1008156921001

Recycled addition of CD4+ T cell-rich population for induction of human autologous cytotoxic T lymphocytes: A practically efficient method

Kaoru Saijo 1, Hideo Tsurushima 1,2, Kouji Tsuboi 2, Tadao Nose 2, Akinori Oki 3, Tadao Ohno 4,✉
PMCID: PMC3449735  PMID: 19003384

Abstract

When CD4+ T cell-rich population appears in theinitial trial in induction cultures of humanautologous cytotoxic T lymphocytes (CTL), the cultureresults frequently in no or weak killing activity andtherefore usually be discarded as an `unsuccessful'CTL induction culture. However, addition of theinitial CD4+ T cell-rich population enabledefficient induction of the autologous CTL in theensuing trials. The CTL thus generated exhibitedstronger killing activities against autologous braintumor cells and ovarian tumor cells than previouslyobserved. This simple recycling of the primed butinert CD4+ T cell-rich population for CTLinduction will promote clinical practice of adoptiveimmunotherapy of human tumors with autologous CTL.

Keywords: adoptive immunotherapy, cytotoxic T lymphocytes, helper T cells, interleukins

Full Text

The Full Text of this article is available as a PDF (101.7 KB).

References

  1. Bennett SR, Carbone FR, Karamalis DF, Miller JF, Heath WR. Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help. J Exp Med. 1997;186:65–70. doi: 10.1084/jem.186.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett SRM, Carbone FR, Karamalis F, Flavell RA, Miller JFAP, Heath WR. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature. 1998;393:478–480. doi: 10.1038/30996. [DOI] [PubMed] [Google Scholar]
  3. Blasczyk R, Hahn U, Wehling J, Huhn D, Salama A. Complete subtyping of the HLA-A locus by sequence-specific amplification followed by direct sequencing or single-strand conformation polymorphism analysis. Tissue Antigens. 1995;46:86–95. doi: 10.1111/j.1399-0039.1995.tb02483.x. [DOI] [PubMed] [Google Scholar]
  4. Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med. 1996;184:747–752. doi: 10.1084/jem.184.2.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Challis GB, Stam HJ. The spontaneous regression of cancer. A review of cases from 1900 to 1987. Acta Oncol. 1990;29:545–550. doi: 10.3109/02841869009090048. [DOI] [PubMed] [Google Scholar]
  6. Chouaib S, Chehimi J, Bani L, Genetet N, Tursz T, Gay F, Trinchieri G, Mami CF. Interleukin 12 induces the differentiation of major histocompatibility complex class I-primed cytotoxic T-lymphocyte precursors into allospecific cytotoxic effectors. Proc Natl Acad Sci U S A. 1994;91:12659–12663. doi: 10.1073/pnas.91.26.12659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Freed SZ, Halperin JP, Gordon M. Idiopathic regression of metastases from renal cell carcinoma. J Urol. 1977;118:538–542. doi: 10.1016/s0022-5347(17)58099-4. [DOI] [PubMed] [Google Scholar]
  8. Goedegebuure PS, Douville CC, Doherty JM, Linehan DC, Lee KY, Ganguly EK, Eberlein TJ. Simultaneous production of T helper-1-like cytokines and cytolytic activity by tumor-specific T cells in ovarian and breast cancer. Cell Immunol. 1997;175:150–156. doi: 10.1006/cimm.1996.1055. [DOI] [PubMed] [Google Scholar]
  9. Halverson DC, Schwartz GN, Carter C, Gress RE, Fowler DH. In vitro generation of allospecific human CD8C T cells of Tc1 and Tc2 phenotype. Blood. 1997;90:2089–2096. [PubMed] [Google Scholar]
  10. Heufler C, Koch F, Stanzl U, Topar G, Wysocka M, Trinchieri G, Enk A, Steinman RM, Romani N, Schuler G. Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol. 1996;26:659–668. doi: 10.1002/eji.1830260323. [DOI] [PubMed] [Google Scholar]
  11. Kawai K, Sasaki T, Saijou K, Akaza H, Koiso K, Ohno T. Additive effects of antitumor drugs and lymphokine-activated killer cell cytotoxic activity in tumor cell killing determined by lactate-dehydrogenase-release assay. Cancer Immunol Immunother. 1992;35:225–229. doi: 10.1007/BF01789327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kohyama M, Saijo K, Hayashida M, Yasugi T, Kurimoto M, Ohno T. Direct activation of human CD8+ cytotoxic T lymphocytes by interleukin-18. Jpn J Cancer Res. 1998;89:1041–1046. doi: 10.1111/j.1349-7006.1998.tb00494.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liu SQ, Saijo K, Todoroki K, Ohno T. Induction of human autologous cytotoxic T lymphocytes on formalin-fixed and paraffin-embedded tumour sections. Nature Med. 1995;1:267–271. doi: 10.1038/nm0395-267. [DOI] [PubMed] [Google Scholar]
  14. Liu SQ, Shiraiwa H, Kawai K, Hayashi H, Akaza H, Hashizaki K, Shiba R, Saijo K, Ohno T. High rate of induction of human autologous cytotoxic T lymphocytes against renal carcinoma cells cultured with an interleukin cocktail. Jpn J Cancer Res. 1998;89:195–201. doi: 10.1111/j.1349-7006.1998.tb00515.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O'Garra A. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol. 1995;154:5071–5079. [PubMed] [Google Scholar]
  16. Ostankovitch M, Le Gal FA, Connan F, Chassin D, Choppin J, Guillet JG. Generation of Melan-A/MART-1-specific CD8+ cytotoxic T lymphocytes from human naive precursors: helper effect requirement for efficient primary cytotoxic T lymphocyte induction in vitro. Int J Cancer. 1997;72:987–994. doi: 10.1002/(sici)1097-0215(19970917)72:6<987::aid-ijc12>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  17. Ossendorf F, Mengé E, Camps M, Filius R, Melief CJM. Specific T helper cell requirement for optimal induction of cytotoxic T lymphocytes against major histocompatibility complex class II negative tumors. J Exp Med. 1998;187:693–702. doi: 10.1084/jem.187.5.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature. 1998;393:474–478. doi: 10.1038/30989. [DOI] [PubMed] [Google Scholar]
  19. Scheicher C, Mehlig M, Dienes HP, Reske K. Uptake of microparticle-adsorbed protein antigen by bone marrow-derived dendritic cells results in up-regulation of interleukin-1 alpha and interleukin-12 p40/p35 and triggers prolonged, efficient antigen presentation. Eur J Immunol. 1995;25:1566–1572. doi: 10.1002/eji.1830250615. [DOI] [PubMed] [Google Scholar]
  20. Shoenberger SP, Toes REM, van der Voort EIH, Offringa R, Melief CJM. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature. 1998;393:480–483. doi: 10.1038/31002. [DOI] [PubMed] [Google Scholar]
  21. Stuhler G, Walden P. Collaboration of helper and cytotoxic T lymphocytes. Eur J Immunol. 1993;23:2279–2286. doi: 10.1002/eji.1830230934. [DOI] [PubMed] [Google Scholar]
  22. Stuhler G, Schlossman SF. Antigen organization regulates cluster formation and induction of cytotoxic T lymphocytes by helper T cell subsets. Proc Natl Acad Sci USA. 1997;94:622–627. doi: 10.1073/pnas.94.2.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsurushima H, Liu SQ, Tsuboi K, Yoshii Y, Nose T, Ohno T. Induction of human cytotoxic T lymphocytes against minced tissues of glioblastoma multiforme. J Neurosurg. 1996;84:258–263. doi: 10.3171/jns.1996.84.2.0258. [DOI] [PubMed] [Google Scholar]

Articles from Cytotechnology are provided here courtesy of Springer Science+Business Media B.V.

RESOURCES