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. 1970 May;6(5):661–670.

In vitro cytoxicity by human lymphocytes from individuals immunized against histocompatibility antigens. I. Kinetics and specificity of the reaction. Influence of metabolic inhibitors and anti-lymphocyte serum

G Lundgren
PMCID: PMC1712718  PMID: 4097827

Abstract

Lymphocytes from humans that had rejected allogeneic skin grafts acquired a cytotoxic potential, which was expressed in vitro upon contact with fibroblast monolayer cultures of the skin donor genotype. No cytotoxic effect was obtained on autochthonous fibroblasts, but did occur on other allogeneic fibroblasts, non-related to the skin donor, suggesting shared histocompatibility antigens. The damage to the target cells developed at the area of lymphocyte application and was detected after 48 hr. The cytotoxic effect of the immune lymphocytes on the specific target cells was suppressed by treatment with actinomycin-C, Mitomycin-C and prednisolone, indicating that cellular synthetic processes and cell divisions are required for cytotoxicity to be expressed. Anti-lymphocyte serum also inhibited the cytotoxic reaction, probably by coating the lymphocyte surface.

In view of previous investigations, concerning cytotoxicity exerted by non-immunized lymphocytes stimulated by non-specific agents, the present results suggest that the specificity of the cytotoxic damage by immunized lymphocytes is confined to the initial immunological recognition of the antigen(s) on the target cells. This reaction triggers the lymphocytes to a cytotoxic state which can be non-specifically expressed. The need for synthetic processes within the lymphocytes may be required for magnifying the process by increasing the number of cytotoxically activated cells and probably also for the continuous synthesis of the antigen-specific receptors.

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Selected References

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

  1. BERG O., KAELLEN B. EFFECT OF MONONUCLEAR BLOOD CELLS FROM MULTIPLE SCLEROSIS PATIENTS ON NEUROGLIA IN TISSUE CULTURE. J Neuropathol Exp Neurol. 1964 Jul;23:550–559. doi: 10.1097/00005072-196407000-00010. [DOI] [PubMed] [Google Scholar]
  2. BRONDZ B. D. INTERACTION OF IMMUNE LYMPHOCYTES IN VITRO WITH NORMAL AND NEOPLASTIC TISSUE CELLS. Folia Biol (Praha) 1964;10:164–176. [PubMed] [Google Scholar]
  3. Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
  4. COULSON A. S., CHALMERS D. G. SEPARATION OF VIABLE LYMPHOCYTES FROM HUMAN BLOOD. Lancet. 1964 Feb 29;1(7331):468–469. doi: 10.1016/s0140-6736(64)90799-8. [DOI] [PubMed] [Google Scholar]
  5. GOVAERTS A. Cellular antibodies in kidney homotransplantation. J Immunol. 1960 Nov;85:516–522. [PubMed] [Google Scholar]
  6. GRANGER G. A., WEISER R. S. HOMOGRAFT TARGET CELLS: SPECIFIC DESTRUCTION IN VITRO BY CONTACT INTERACTION WITH IMMUNE MACROPHAGES. Science. 1964 Sep 25;145(3639):1427–1429. doi: 10.1126/science.145.3639.1427. [DOI] [PubMed] [Google Scholar]
  7. Granger G. A., Williams T. W. Lymphocyte cytotoxicity in vitro: activation and release of a cytotoxic factor. Nature. 1968 Jun 29;218(5148):1253–1254. doi: 10.1038/2181253a0. [DOI] [PubMed] [Google Scholar]
  8. HEDBERG H., KAELLEN B. STUDIES ON MONONUCLEAR CELLS OBTAINED FROM SYNOVIAL FLUID OF PATIENTS WITH DIFFERENT TYPES OF ARTHRITIS. CYTOTOXIC EFFECT ON TISSUE-CULTURED HUMAN FIBROBLASTS. Acta Pathol Microbiol Scand. 1964;62:177–188. doi: 10.1111/apm.1964.62.2.177. [DOI] [PubMed] [Google Scholar]
  9. HOLM G., PERLMANN P., WERNER B. PHYTOHAEMAGGLUTININ-INDUCED CYTOTOXIC ACTION OF NORMAL LYMPHOID CELLS ON CELLS IN TISSUE CULTURE. Nature. 1964 Aug 22;203:841–843. doi: 10.1038/203841a0. [DOI] [PubMed] [Google Scholar]
  10. Lundgren G., Collste L., Möller G. Cytotoxicity of human lymphocytes: antagonism between inducing processes. Nature. 1968 Oct 19;220(5164):289–291. doi: 10.1038/220289a0. [DOI] [PubMed] [Google Scholar]
  11. Lundgren G., Möller E., Thorsby E. In vitro cytotoxicity by human lymphocytes from individuals immunized against histocompatibility antigens. II. Relation to HL-A incompatibility between effector and target cells. Clin Exp Immunol. 1970 May;6(5):671–680. [PMC free article] [PubMed] [Google Scholar]
  12. Lundgren G., Möller G. Non-specific induction of cytotoxicity in normal human lymphocytes in vitro: studies of mechanism and specificity of the reaction. Clin Exp Immunol. 1969 Apr;4(4):435–452. [PMC free article] [PubMed] [Google Scholar]
  13. Lundgren G., Zukoski C. F., Möller G. Differential effects of human granulocytes and lymphocytes on human fibroblasts in vitro. Clin Exp Immunol. 1968 Oct;3(8):817–836. [PMC free article] [PubMed] [Google Scholar]
  14. MOELLER E. ANTAGONISTIC EFFECTS OF HUMORAL ISOANTIBODIES ON THE IN VITRO CYTOTOXICITY OF IMMUNE LYMPHOID CELLS. J Exp Med. 1965 Jul 1;122:11–23. doi: 10.1084/jem.122.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. PERLMANN P., BROBERGER O. In vitro studies of ulcerative colitis. II. Cytotoxic action of white blood cells from patients on human fetal colon cells. J Exp Med. 1963 May 1;117:717–733. doi: 10.1084/jem.117.5.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. REICH E., FRANKLIN R. M., SHATKIN A. J., TATUM E. L. Effect of actinomycin D on cellular nucleic acid synthesis and virus production. Science. 1961 Aug 25;134(3478):556–557. doi: 10.1126/science.134.3478.556. [DOI] [PubMed] [Google Scholar]
  17. ROSENAU W., MOON H. D. Lysis of homologous cells by sensitized lymphocytes in tissue culture. J Natl Cancer Inst. 1961 Aug;27:471–483. [PubMed] [Google Scholar]
  18. Ruddle N. H., Waksman B. H. Cytotoxic effect of lymphocyte-antigen interaction in delayed hypersensitivity. Science. 1967 Sep 1;157(3792):1060–1062. doi: 10.1126/science.157.3792.1060. [DOI] [PubMed] [Google Scholar]
  19. Ruddle N. H., Waksman B. H. Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. 3. Analysis of mechanism. J Exp Med. 1968 Dec 1;128(6):1267–1279. doi: 10.1084/jem.128.6.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ruddle N. H., Waksman B. H. Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. I. Characterization of the phenomenon. J Exp Med. 1968 Dec 1;128(6):1237–1254. doi: 10.1084/jem.128.6.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sukernick R., Hanin A., Mosolov A. The reaction of blood lymphocytes from patients with rheumatoid arthritis against human connective tissue cells in vitro. Clin Exp Immunol. 1968 Feb;3(2):171–177. [PMC free article] [PubMed] [Google Scholar]
  22. Traeger J., Carraz M., Fries D., Perrin J., Saubier E., Bernhardt J. P., Revillard J. P., Bonnet P., Archimbaud J. P., Brochier J. Studies of anti-lymphocyte globulins made from thoracic duct lymphocytes. Transplant Proc. 1969 Mar;1(1):455–459. [PubMed] [Google Scholar]
  23. Trayanova T. G., Sura V. V., Svet-Moldavsky G. J. Destruction of human cells in tissue culture by lymphocytes from patients with systemic lupus erythematosus. Lancet. 1966 Feb 26;1(7435):452–454. doi: 10.1016/s0140-6736(66)91456-5. [DOI] [PubMed] [Google Scholar]
  24. WILSON D. B. QUANTITATIVE STUDIES ON THE BEHAVIOR OF SENSITIZED LYMPHOCYTES IN VITRO. II. INHIBITORY INFLUENCE OF THE IMMUNE SUPPRESSOR, IMURAN, ON THE DESTRUCTIVE REACTION OF SENSITIZED LYMPHOID CELLS AGAINST HOMOLOGOUS TARGET CELLS. J Exp Med. 1965 Jul 1;122:167–172. doi: 10.1084/jem.122.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. WILSON D. B. THE REACTION OF IMMUNOLOGICALLY ACTIVATED LYMPHOID CELLS AGAINST HOMOLOGOUS LYMPHOID CELLS AGAINST HOMOLOGOUS TARGET TISSUE CELLS IN VITRO. J Cell Physiol. 1963 Dec;62:273–286. doi: 10.1002/jcp.1030620307. [DOI] [PubMed] [Google Scholar]
  26. WOODRUFF M. F., ANDERSON N. A. EFFECT OF LYMPHOCYTE DEPLETION BY THORACIC DUCT FISTULA AND ADMINISTRATION OF ANTILYMPHOCYTIC SERUM ON THE SURVIVAL OF SKIN HOMOGRAFTS IN RATS. Nature. 1963 Nov 16;200:702–702. doi: 10.1038/200702a0. [DOI] [PubMed] [Google Scholar]

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