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J Exp Med. 1993 Jan 1; 177(1): 155–164.
PMCID: PMC2190856

The development of autoimmunity in C57BL/6 lpr mice correlates with the disappearance of natural killer type 1-positive cells: evidence for their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms


F1 hybrid mice are able to acutely reject parental marrow grafts, a phenomenon that is due to natural killer type 1-positive (NK1+) cells. Circumstantial evidence had suggested that the antigenic determinants recognized by these cells are self-antigens, leading to the hypothesis that the physiological role of NK1+ cells is a downregulatory or suppressive function on bone marrow stem cell proliferation and lymphocyte function. In analyzing this hypothesis it is shown here that in young mice there is a temporal correlation between appearance of NK1+ cells in the spleen and the ability to reject allogeneic marrow or to suppress endogenous stem cell proliferation. The reverse situation exists in mice expressing the homozygous lpr gene. Whereas in young mice cells with NK1+ phenotype are demonstrable, these cells disappear with age, i.e., at the time autoimmunity develops. Concomitant with the disappearance of NK1+ cells, the ability to reject marrow grafts and to control endogenous stem cell proliferation also vanishes. The suggestion that the development of autoimmunity is causally related to the disappearance of NK1+ cells is supported by experiments in which NK1+ cells were either eliminated by antibody injection or increased by adoptively transferring cell populations enriched for NK1+ cells into lpr mice. It is shown that removal of cells enhances autoimmunity, whereas injection of NK1+ cells delays the onset of autoimmunity. In vitro assays are presented that demonstrate that suppression of autoantibody-secreting B cells is due to two NK1+ cell populations, one that expresses CD3 and causes specific suppression and one that lacks CD3 and causes nonspecific suppression.

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Selected References

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  • Yankelevich B, Knobloch C, Nowicki M, Dennert G. A novel cell type responsible for marrow graft rejection in mice. T cells with NK phenotype cause acute rejection of marrow grafts. J Immunol. 1989 May 15;142(10):3423–3430. [PubMed]
  • Blazar BR, Hirsch R, Gress RE, Carroll SF, Vallera DA. In vivo administration of anti-CD3 monoclonal antibodies or immunotoxins in murine recipients of allogeneic T cell-depleted marrow for the promotion of engraftment. J Immunol. 1991 Sep 1;147(5):1492–1503. [PubMed]
  • Kikly K, Dennert G. Evidence for extrathymic development of TNK cells. NK1+ CD3+ cells responsible for acute marrow graft rejection are present in thymus-deficient mice. J Immunol. 1992 Jul 15;149(2):403–412. [PubMed]
  • Murphy WJ, Kumar V, Bennett M. Rejection of bone marrow allografts by mice with severe combined immune deficiency (SCID). Evidence that natural killer cells can mediate the specificity of marrow graft rejection. J Exp Med. 1987 Apr 1;165(4):1212–1217. [PMC free article] [PubMed]
  • Nowicki M, Yankelevich B, Kikly K, Dennert G. Induction of tolerance to parental marrow grafts in F1 hybrid mice. Evidence for recognition of self-antigens. J Immunol. 1990 Jan 1;144(1):47–52. [PubMed]
  • Scribner CL, Steinberg AD. The role of splenic colony-forming units in autoimmune disease. Clin Immunol Immunopathol. 1988 Oct;49(1):133–142. [PubMed]
  • TILL JE, McCULLOCH EA. Early repair processes in marrow cells irradiated and proliferating in vivo. Radiat Res. 1963 Jan;18:96–105. [PubMed]
  • Knobloch C, Dennert G. Loss of F1 hybrid resistance to bone marrow grafts after injection of parental lymphocytes. Demonstration of parental anti-F1 T killer cells and general immunosuppression in the host. Transplantation. 1988 Jan;45(1):175–183. [PubMed]
  • Koo GC, Dumont FJ, Tutt M, Hackett J, Jr, Kumar V. The NK-1.1(-) mouse: a model to study differentiation of murine NK cells. J Immunol. 1986 Dec 15;137(12):3742–3747. [PubMed]
  • Mage MG, McHugh LL, Rothstein TL. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. [PubMed]
  • Dennert G, Hyman R, Lesley J, Trowbridge IS. Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. Cell Immunol. 1980 Aug 1;53(2):350–364. [PubMed]
  • Koo GC, Peppard JR. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 1984 Fall;3(3):301–303. [PubMed]
  • Havran WL, Poenie M, Kimura J, Tsien R, Weiss A, Allison JP. Expression and function of the CD3-antigen receptor on murine CD4+8+ thymocytes. Nature. 1987 Nov 12;330(6144):170–173. [PubMed]
  • Raulet DH, Gottlieb PD, Bevan MJ. Fractionation of lymphocyte populations with monoclonal antibodies specific for LYT-2.2 and LYT-3.1. J Immunol. 1980 Sep;125(3):1136–1143. [PubMed]
  • Coffman RL, Weissman IL. B220: a B cell-specific member of th T200 glycoprotein family. Nature. 1981 Feb 19;289(5799):681–683. [PubMed]
  • Ando DG, Ebling FM, Hahn BH. Detection of native and denatured DNA antibody forming cells by the enzyme-linked immunospot assay. A clinical study of (New Zealand black x New Zealand white)F1 mice. Arthritis Rheum. 1986 Sep;29(9):1139–1146. [PubMed]
  • Ando DG, Sercarz EE, Hahn BH. Mechanisms of T and B cell collaboration in the in vitro production of anti-DNA antibodies in the NZB/NZW F1 murine SLE model. J Immunol. 1987 May 15;138(10):3185–3190. [PubMed]
  • Carlsten H, Tarkowski A. Expression of heterozygous lpr gene in MRL mice. I. Defective T-cell reactivity and polyclonal B-cell activation. Scand J Immunol. 1989 Oct;30(4):457–462. [PubMed]
  • Bennett M. Biology and genetics of hybrid resistance. Adv Immunol. 1987;41:333–445. [PubMed]
  • Ballas ZK, Rasmussen W. Lymphokine-activated killer (LAK) cells. VI. NK1.1+, CD3+ LAK effectors are derived from CD4-, CD8-, NK1.1- precursors. Cell Immunol. 1991 May;134(2):296–313. [PubMed]
  • Abruzzo LV, Rowley DA. Homeostasis of the antibody response: immunoregulation by NK cells. Science. 1983 Nov 11;222(4624):581–585. [PubMed]
  • Hansson M, Petersson M, Koo GC, Wigzell H, Kiessling R. In vivo function of natural killer cells as regulators of myeloid precursor cells in the spleen. Eur J Immunol. 1988 Mar;18(3):485–488. [PubMed]

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