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. 1993 Sep;61(9):3769–3774. doi: 10.1128/iai.61.9.3769-3774.1993

Natural killer cells do not play a dominant role in CD4+ subset differentiation in Candida albicans-infected mice.

L Romani 1, A Mencacci 1, E Cenci 1, R Spaccapelo 1, E Schiaffella 1, L Tonnetti 1, P Puccetti 1, F Bistoni 1
PMCID: PMC281076  PMID: 8359898

Abstract

The effects of in vivo administration of monoclonal antibodies against NK-1.1-bearing cells on the early production of gamma interferon (IFN-gamma) in vitro and development of Th1-associated immunity were studied in mice infected with a live vaccine strain of Candida albicans. At 1 and 4 days postinfection, natural killer (NK) cell-enriched fractions from the spleens of antibody-treated mice displayed a dramatic reduction in 5E6+ lymphocytes and negligible anti-YAC-1 cytotoxic activity in vitro. Nevertheless, the frequency of IFN-gamma-producing cells in those fractions was reduced by less than half, on average, by anti-NK-1.1 treatment in vivo. In addition, the antibody-treated and infected mice demonstrated unchanged T helper cell responses, as measured by yeast-specific footpad reactions, resistance to reinfection, occurrence of antibodies of different isotypes, and production in vitro of interleukin-2 (IL-2), IFN-gamma, IL-4, and IL-10 by CD4+ cells. Therefore, although NK cells may contribute to early IFN-gamma production in Candida-vaccinated mice, these cells apparently do not play a dominant role in the qualitative development of yeast-specific T helper responses.

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Selected References

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

  1. Ashman R. B., Papadimitriou J. M. Susceptibility of beige mutant mice to candidiasis may be linked to a defect in granulocyte production by bone marrow stem cells. Infect Immun. 1991 Jun;59(6):2140–2146. doi: 10.1128/iai.59.6.2140-2146.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baccarini M., Bistoni F., Puccetti P., Garaci E. Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector. Infect Immun. 1983 Oct;42(1):1–9. doi: 10.1128/iai.42.1.1-9.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baghian A., Lee K. W. Systemic candidosis in beige mice. J Med Vet Mycol. 1989;27(1):51–55. doi: 10.1080/02681218980000071. [DOI] [PubMed] [Google Scholar]
  4. Beno D. W., Mathews H. L. Growth inhibition of Candida albicans by interleukin-2-activated splenocytes. Infect Immun. 1992 Mar;60(3):853–863. doi: 10.1128/iai.60.3.853-863.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cantorna M. T., Balish E. Acquired immunity to systemic candidiasis in immunodeficient mice. J Infect Dis. 1991 Nov;164(5):936–943. doi: 10.1093/infdis/164.5.936. [DOI] [PubMed] [Google Scholar]
  6. Cenci E., Romani L., Mencacci A., Spaccapelo R., Schiaffella E., Puccetti P., Bistoni F. Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing of Candida albicans. Eur J Immunol. 1993 May;23(5):1034–1038. doi: 10.1002/eji.1830230508. [DOI] [PubMed] [Google Scholar]
  7. Cenci E., Romani L., Vecchiarelli A., Puccetti P., Bistoni F. Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice. Infect Immun. 1989 Nov;57(11):3581–3587. doi: 10.1128/iai.57.11.3581-3587.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cenci E., Romani L., Vecchiarelli A., Puccetti P., Bistoni F. T cell subsets and IFN-gamma production in resistance to systemic candidosis in immunized mice. J Immunol. 1990 Jun 1;144(11):4333–4339. [PubMed] [Google Scholar]
  9. Djeu J. Y., Blanchard D. K., Halkias D., Friedman H. Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. J Immunol. 1986 Nov 1;137(9):2980–2984. [PubMed] [Google Scholar]
  10. Djeu J. Y., Blanchard D. K., Richards A. L., Friedman H. Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes. J Immunol. 1988 Dec 1;141(11):4047–4052. [PubMed] [Google Scholar]
  11. Hector R. F., Domer J. E., Carrow E. W. Immune responses to Candida albicans in genetically distinct mice. Infect Immun. 1982 Dec;38(3):1020–1028. doi: 10.1128/iai.38.3.1020-1028.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jensen J., Vazquez-Torres A., Balish E. Poly(I.C)-induced interferons enhance susceptibility of SCID mice to systemic candidiasis. Infect Immun. 1992 Nov;60(11):4549–4557. doi: 10.1128/iai.60.11.4549-4557.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koo G. C., Peppard J. R. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 1984 Fall;3(3):301–303. doi: 10.1089/hyb.1984.3.301. [DOI] [PubMed] [Google Scholar]
  14. Morelli L., Lusignan Y., Lemieux S. Heterogeneity of natural killer cell subsets in NK-1.1+ and NK-1.1- inbred mouse strains and their progeny. Cell Immunol. 1992 Apr 15;141(1):148–160. doi: 10.1016/0008-8749(92)90134-b. [DOI] [PubMed] [Google Scholar]
  15. Mosmann T. R., Coffman R. L. Heterogeneity of cytokine secretion patterns and functions of helper T cells. Adv Immunol. 1989;46:111–147. doi: 10.1016/s0065-2776(08)60652-5. [DOI] [PubMed] [Google Scholar]
  16. Nabavi N., Murphy J. W. In vitro binding of natural killer cells to Cryptococcus neoformans targets. Infect Immun. 1985 Oct;50(1):50–57. doi: 10.1128/iai.50.1.50-57.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. doi: 10.1016/0167-5699(92)90083-J. [DOI] [PubMed] [Google Scholar]
  18. Romani L., Cenci E., Mencacci A., Spaccapelo R., Grohmann U., Puccetti P., Bistoni F. Gamma interferon modifies CD4+ subset expression in murine candidiasis. Infect Immun. 1992 Nov;60(11):4950–4952. doi: 10.1128/iai.60.11.4950-4952.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Romani L., Mencacci A., Cenci E., Mosci P., Vitellozzi G., Grohmann U., Puccetti P., Bistoni F. Course of primary candidiasis in T cell-depleted mice infected with attenuated variant cells. J Infect Dis. 1992 Dec;166(6):1384–1392. doi: 10.1093/infdis/166.6.1384. [DOI] [PubMed] [Google Scholar]
  20. Romani L., Mencacci A., Cenci E., Spaccapelo R., Mosci P., Puccetti P., Bistoni F. CD4+ subset expression in murine candidiasis. Th responses correlate directly with genetically determined susceptibility or vaccine-induced resistance. J Immunol. 1993 Feb 1;150(3):925–931. [PubMed] [Google Scholar]
  21. Romani L., Mencacci A., Grohmann U., Mocci S., Mosci P., Puccetti P., Bistoni F. Neutralizing antibody to interleukin 4 induces systemic protection and T helper type 1-associated immunity in murine candidiasis. J Exp Med. 1992 Jul 1;176(1):19–25. doi: 10.1084/jem.176.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Romani L., Mocci S., Bietta C., Lanfaloni L., Puccetti P., Bistoni F. Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance. Infect Immun. 1991 Dec;59(12):4647–4654. doi: 10.1128/iai.59.12.4647-4654.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Romani L., Mocci S., Cenci E., Rossi R., Puccetti P., Bistoni F. Candida albicans-specific Ly-2+ lymphocytes with cytolytic activity. Eur J Immunol. 1991 Jun;21(6):1567–1570. doi: 10.1002/eji.1830210636. [DOI] [PubMed] [Google Scholar]
  24. Seaman W. E., Sleisenger M., Eriksson E., Koo G. C. Depletion of natural killer cells in mice by monoclonal antibody to NK-1.1. Reduction in host defense against malignancy without loss of cellular or humoral immunity. J Immunol. 1987 Jun 15;138(12):4539–4544. [PubMed] [Google Scholar]
  25. Sentman C. L., Hackett J., Jr, Kumar V., Bennett M. Identification of a subset of murine natural killer cells that mediates rejection of Hh-1d but not Hh-1b bone marrow grafts. J Exp Med. 1989 Jul 1;170(1):191–202. doi: 10.1084/jem.170.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Varkila K., Chatelain R., Leal L. M., Coffman R. L. Reconstitution of C.B-17 scid mice with BALB/c T cells initiates a T helper type-1 response and renders them capable of healing Leishmania major infection. Eur J Immunol. 1993 Jan;23(1):262–268. doi: 10.1002/eji.1830230141. [DOI] [PubMed] [Google Scholar]
  27. Vecchiarelli A., Cenci E., Puliti M., Blasi E., Puccetti P., Cassone A., Bistoni F. Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state. Cell Immunol. 1989 Dec;124(2):334–344. doi: 10.1016/0008-8749(89)90135-4. [DOI] [PubMed] [Google Scholar]
  28. Zunino S. J., Hudig D. Interactions between human natural killer (NK) lymphocytes and yeast cells: human NK cells do not kill Candida albicans, although C. albicans blocks NK lysis of K562 cells. Infect Immun. 1988 Mar;56(3):564–569. doi: 10.1128/iai.56.3.564-569.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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