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Clin Exp Immunol. Dec 1990; 82(3): 527–532.
PMCID: PMC1535512

Persistence of allospecific helper T cells is required for maintaining autoantibody formation in lupus-like graft-versus-host disease.


Induction of a graft-versus-host (GVH) reaction (GVHR) in non-irradiated (C57BL/10ScSn x DBA/2)F1 mice (BDF1) with DBA/2 lymphoid cells leads to chronic GVH disease (GVHD). One of the pathological alterations of this type of GVHD is hyperplasia of host B cells with production of lupus-like autoantibodies. This hyperstimulation of host B cells has previously been demonstrated to be induced by alloreactive donor T helper cells that were also proposed to maintain it. We provide three pieces of experimental evidence in support of this concept. First, treatment of mice with chronic GVHD by injection of monoclonal anti-Thy-1.2 antibodies, performed at week 6 after the injection of C57BL/6 lymphoid cells into (C57BL/6 x C57BL.bm12)F1 mice led to a significant decrease in the titre of anti-nuclear antibodies. Second, CD4+ donor T cells persisted in BDF1 mice with GVHD (GVHF1) for at least 10 weeks after the induction of GVHR; these T cells showed alloreactive helper activity against H-2b MHC determinants of the opposite parent in vitro. Third, T cells of GVHF1 mice, obtained 2 months after the induction of GVHR and transferred into normal secondary recipients, induced signs of chronic GVHD in DBF1 but not in DBA/2 mice. The combined results show that persisting donor T helper cells in GVHF1 mice retain their alloreactivity towards H-2 class II antigens for a long time after the induction of GVHR and they strongly suggest that these T cells are also the driving force behind the production of lupus-like autoantibodies at the late stage of chronic GVHD.

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  • Abramowicz D, Van der Vorst P, Bruyns C, Lambert P, Goldman M. Autoimmunity and glomerulonephritis after neonatal induction of lymphoid chimerism in mice: role of donor B cells and host T cells. Nephrol Dial Transplant. 1988;3(4):399–404. [PubMed]
  • Del Guercio P, Motta I, Metezeau P, Brugere S, Perret R, Truffa-Bachi P. Heterogeneity of mouse Thy 1.2 antigen expression revealed by monoclonal antibodies. Cell Immunol. 1982 Oct;73(1):72–82. [PubMed]
  • Dziarski R. Autoimmunity: polyclonal activation or antigen induction? Immunol Today. 1988 Nov;9(11):340–342. [PubMed]
  • Gleichmann E, Gleichmann H, Wilke W. Autoimmunization and lymphomagenesis in parent to F1 combinations differing at the major histocompatibility complex: model for spontaneous disease caused by altered self-antigens? Transplant Rev. 1976;31:156–224. [PubMed]
  • Goldman M, Feng HM, Engers H, Hochman A, Louis J, Lambert PH. Autoimmunity and immune complex disease after neonatal induction of transplantation tolerance in mice. J Immunol. 1983 Jul;131(1):251–258. [PubMed]
  • Miller SM, Gupta R, Lee SH, Belitsky P. Renal allograft rejection induces MHC class II upregulation in autologous kidney and liver of the recipient. Transplant Proc. 1989 Feb;21(1 Pt 1):328–328. [PubMed]
  • Kimura M, van Rappard-van der Veen FM, Gleichmann E. Requirement of H-2-subregion differences for graft-versus-host autoimmunity in mice: superiority of the differences at class-II H-2 antigens (I-A/I-E). Clin Exp Immunol. 1986 Sep;65(3):542–552. [PMC free article] [PubMed]
  • Klinman DM, Ishigatsubo Y, Steinberg AD. Acquisition and maturation of expressed B cell repertoires in normal and autoimmune mice. J Immunol. 1988 Aug 1;141(3):801–806. [PubMed]
  • Kuppers RC, Suiter T, Gleichmann E, Rose NR. The induction of organ-specific antibodies during the graft-vs.-host reaction. Eur J Immunol. 1988 Jan;18(1):161–166. [PubMed]
  • Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, Waltersdorph AM. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed]
  • McKenzie IF, Morgan GM, Sandrin MS, Michaelides MM, Melvold RW, Kohn HI. B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse. J Exp Med. 1979 Dec 1;150(6):1323–1338. [PMC free article] [PubMed]
  • Moser M, Mizuochi T, Sharrow SO, Singer A, Shearer GM. Graft-vs-host reaction limited to a class II MHC difference results in a selective deficiency in L3T4+ but not in Lyt-2+ T helper cell function. J Immunol. 1987 Mar 1;138(5):1355–1362. [PubMed]
  • Naparstek Y, André-Schwartz J, Manser T, Wysocki LJ, Breitman L, Stollar BD, Gefter M, Schwartz RS. A single germline VH gene segment of normal A/J mice encodes autoantibodies characteristic of systemic lupus erythematosus. J Exp Med. 1986 Aug 1;164(2):614–626. [PMC free article] [PubMed]
  • Opitz HG, Opitz U, Hewlett G, Schlumberger HD. A new model for investigations of T-cell functions in mice: differential immunosuppressive effects of two monoclonal anti-Thy-1.2 antibodies. Immunobiology. 1982 Feb;160(5):438–453. [PubMed]
  • Pals ST, Gleichmann H, Gleichmann E. Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. V. F1 mice with secondary chronic GVHD contain F1-reactive allohelper but no allosuppressor T cells. J Exp Med. 1984 Feb 1;159(2):508–523. [PMC free article] [PubMed]
  • Pals ST, Radaszkiewicz T, Gleichmann E. Allosuppressor- and allohelper-T cells in acute and chronic graft-vs-host disease. IV. Activation of donor allosuppressor cells is confined to acute GVHD. J Immunol. 1984 Apr;132(4):1669–1678. [PubMed]
  • Pals ST, Radaszkiewicz T, Roozendaal L, Gleichmann E. Chronic progressive polyarthritis and other symptoms of collagen vascular disease induced by graft-vs-host reaction. J Immunol. 1985 Mar;134(3):1475–1482. [PubMed]
  • Rolink AG, Pals ST, Gleichmann E. Allosuppressor and allohelper T cells in acute and chronic graft-vs.-host disease. II. F1 recipients carrying mutations at H-2K and/or I-A. J Exp Med. 1983 Feb 1;157(2):755–771. [PMC free article] [PubMed]
  • Rolink AG, Gleichmann E. Allosuppressor- and allohelper-T cells in acute and chronic graft-vs.-host (GVH) disease. III. Different Lyt subsets of donor T cells induce different pathological syndromes. J Exp Med. 1983 Aug 1;158(2):546–558. [PMC free article] [PubMed]
  • Rolink AG, Gleichmann H, Gleichmann E. Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. VII. Immune-complex glomerulonephritis. J Immunol. 1983 Jan;130(1):209–215. [PubMed]
  • Rolink AG, Radaszkiewicz T, Melchers F. The autoantigen-binding B cell repertoires of normal and of chronically graft-versus-host-diseased mice. J Exp Med. 1987 Jun 1;165(6):1675–1687. [PMC free article] [PubMed]
  • Van Rappard-Van Der Veen FM, Radaszkiewicz T, Terraneo L, Gleichmann E. Attempts at standardization of lupus-like graft-vs-host disease: inadvertent repopulation by DBA/2 spleen cells of H-2-different nonirradiated F1 mice. J Immunol. 1983 Jun;130(6):2693–2701. [PubMed]
  • van Rappard-van der Veen FM, Kong YM, Rose NR, Kimura M, Gleichmann E. Injection of mouse thyroglobulin and/or adult thymectomy do not break tolerance to thyroglobulin during the lupus like graft versus host disease in mice. Clin Exp Immunol. 1984 Mar;55(3):525–534. [PMC free article] [PubMed]
  • Via CS, Shearer GM. T-cell interactions in autoimmunity: insights from a murine model of graft-versus-host disease. Immunol Today. 1988 Jul-Aug;9(7-8):207–213. [PubMed]
  • Via CS, Sharrow SO, Shearer GM. Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occurring in a murine model of graft-vs-host disease. J Immunol. 1987 Sep 15;139(6):1840–1849. [PubMed]

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