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. 1980 May 1;151(5):1039–1048. doi: 10.1084/jem.151.5.1039

Chediak-Higashi gene in humans. I. Impairment of natural - killer function

T Haliotis, J Roder, M Klein, J Ortaldo, AS Fauci, RB Herberman
PMCID: PMC2185857  PMID: 6154765

Abstract

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.

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Selected References

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

  1. Ackerman S. K., Douglas S. D. Purification of human monocytes on microexudate-coated surfaces. J Immunol. 1978 Apr;120(4):1372–1374. [PubMed] [Google Scholar]
  2. Alexander E., Henkart P. The adherence of human Fc receptor-bearing lymphocytes to antigen-antibody complexes. II. Morphologic alterations induced by the substrate. J Exp Med. 1976 Feb 1;143(2):329–347. doi: 10.1084/jem.143.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blume R. S., Wolff S. M. The Chediak-Higashi syndrome: studies in four patients and a review of the literature. Medicine (Baltimore) 1972 Jul;51(4):247–280. [PubMed] [Google Scholar]
  4. Cudkowicz G., Hochman P. S. Do natural killer cells engage in regulated reactions against self to ensure homeostasis? Immunol Rev. 1979;44:13–41. doi: 10.1111/j.1600-065x.1979.tb00266.x. [DOI] [PubMed] [Google Scholar]
  5. Dent P. B., Fish L. A., White L. G., Good R. A. Chediak-Higashi syndrome. Observations on the nature of the associated malignancy. Lab Invest. 1966 Oct;15(10):1634–1642. [PubMed] [Google Scholar]
  6. Gallin J. I., Elin R. J., Hubert R. T., Fauci A. S., Kaliner M. A., Wolff S. M. Efficacy of ascorbic acid in Chediak-Higashi syndrome (CHS): studies in humans and mice. Blood. 1979 Feb;53(2):226–234. [PubMed] [Google Scholar]
  7. Gidlund M., Orn A., Wigzell H., Senik A., Gresser I. Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature. 1978 Jun 29;273(5665):759–761. doi: 10.1038/273759a0. [DOI] [PubMed] [Google Scholar]
  8. Haller O., Hansson M., Kiessling R., Wigzell H. Role of non-conventional natural killer cells in resistance against syngeneic tumour cells in vivo. Nature. 1977 Dec 15;270(5638):609–611. doi: 10.1038/270609a0. [DOI] [PubMed] [Google Scholar]
  9. Herberman R. R., Ortaldo J. R., Bonnard G. D. Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature. 1979 Jan 18;277(5693):221–223. doi: 10.1038/277221a0. [DOI] [PubMed] [Google Scholar]
  10. Klein M., Roder J., Haliotis T., Korec S., Jett J. R., Herberman R. B., Katz P., Fauci A. S. Chédiak-Higashi gene in humans. II. The selectivity of the defect in natural-killer and antibody-dependent cell-mediated cytotoxicity function. J Exp Med. 1980 May 1;151(5):1049–1058. doi: 10.1084/jem.151.5.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koren H. S., Amos D. B., Buckley R. H. Natural killing in immunodeficient patients. J Immunol. 1978 Mar;120(3):796–799. [PubMed] [Google Scholar]
  12. Lohmann-Matthes M. L., Domzig W., Roder J. Promonocytes have the functional characteristics of natural killer cells. J Immunol. 1979 Oct;123(4):1883–1886. [PubMed] [Google Scholar]
  13. Ortaldo J. R., Bonnard G. D., Kind P. D., Herberman R. B. Cytotoxicity by cultured human lymphocytes: characteristics of effector cells and specificity of cytotoxicity. J Immunol. 1979 Apr;122(4):1489–1494. [PubMed] [Google Scholar]
  14. Pross H. F., Gupta S., Good R. A., Baines M. G. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. VII. The effect of immunodeficiency disease. Cell Immunol. 1979 Mar 1;43(1):160–175. doi: 10.1016/0008-8749(79)90159-x. [DOI] [PubMed] [Google Scholar]
  15. Roder J. C., Ahrlund-Richter L., Jondal M. Target-effector interaction in the human and murine natural killer system: specificity and xenogeneic reactivity of the solubilized natural killer-target structure complex and its loss in a somatic cell hybrid. J Exp Med. 1979 Sep 19;150(3):471–481. doi: 10.1084/jem.150.3.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Roder J. C., Kiessling R., Biberfeld P., Andersson B. Target-effector interaction in the natural killer (NK) cell system. II. The isolation of NK cells and studies on the mechanism of killing. J Immunol. 1978 Dec;121(6):2509–2517. [PubMed] [Google Scholar]
  17. Roder J. C., Kiessling R. Target--effector interaction in the natural killer cell system. I. Covariance and genetic control of cytolytic and target-cell-binding subpopulations in the mouse. Scand J Immunol. 1978;8(2):135–144. doi: 10.1111/j.1365-3083.1978.tb00505.x. [DOI] [PubMed] [Google Scholar]
  18. Roder J., Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature. 1979 Mar 29;278(5703):451–453. doi: 10.1038/278451a0. [DOI] [PubMed] [Google Scholar]
  19. Root R. K., Rosenthal A. S., Balestra D. J. Abnormal bactericidal, metabolic, and lysosomal functions of Chediak-Higashi Syndrome leukocytes. J Clin Invest. 1972 Mar;51(3):649–665. doi: 10.1172/JCI106854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Windhorst D. B., Padgett G. The Chediak-Higashi syndrome and the homologous trait in animals. J Invest Dermatol. 1973 Jun;60(6):529–537. doi: 10.1111/1523-1747.ep12703609. [DOI] [PubMed] [Google Scholar]

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