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J Exp Med. 1988 March 1; 167(3): 741–751.
PMCID: PMC2188886

The lpr gene causes an intrinsic T cell abnormality that is required for hyperproliferation


The lpr gene induces marked lymphoproliferation characterized by the massive accumulation of T cells of an unusual phenotype and concomitant autoimmune disease. To clarify the mechanism of the lpr effect, bone marrow cells from B6-lpr/lpr (Ly-1.2) and B6-+/+ (Ly-1.1) mice were transferred into lethally irradiated B6-lpr/lpr mice. As has been previously reported, recipients of the B6-lpr/lpr bone marrow showed the typical lpr phenotype with marked lymphadenopathy, splenomegaly and increased levels of autoantibodies; while the recipients of B6-+/+ bone marrow had normal sized lymph nodes and spleen and no autoantibodies. A third group of mice received an equal mixture of bone marrow cells from the B6-lpr/lpr and B6-+/+ donors. These mice showed both lymphadenopathy and autoantibody production comparable to that of recipients of the B6-lpr/lpr marrow alone. Immunofluorocytometric analysis of the lymphoid populations in these mixed bone marrow recipients established that the T cells from the lpr/lpr and +/+ donors were equivalently represented in the peripheral blood and thymus. In striking contrast, the T cells that accumulated in abnormally large numbers in the lymph nodes were almost entirely from the lpr donor. Their surface phenotype was Thy-1+(dull), Ly-1.2+(dull), Lyt-2-, L3T4-, 9F3+, and 3A1+, which is consistent with that found in intact lpr mice. These results indicate that the lpr gene causes an intrinsic defect directly within the T cells that accumulate in large numbers in lpr mice. In addition, the presence of the +/+ T cells cannot prevent the expression of the lpr abnormalities.

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Selected References

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  • Pisetsky DS, Caster SA, Roths JB, Murphy ED. Ipr gene control of the anti-DNA antibody response. J Immunol. 1982 May;128(5):2322–2325. [PubMed]
  • Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. [PubMed]
  • Davidson WF, Dumont FJ, Bedigian HG, Fowlkes BJ, Morse HC., 3rd Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J Immunol. 1986 Jun 1;136(11):4075–4084. [PubMed]
  • Mountz JD, Huppi KE, Seldin MF, Mushinski JF, Steinberg AD. T cell receptor gene expression in autoimmune mice. J Immunol. 1986 Aug 1;137(3):1029–1036. [PubMed]
  • Morse HC, 3rd, Davidson WF, Yetter RA, Murphy ED, Roths JB, Coffman RL. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol. 1982 Dec;129(6):2612–2615. [PubMed]
  • Lewis DE, Giorgi JV, Warner NL. Flow cytometry analysis of T cells and continuous T-cell lines from autoimmune MRL/l mice. Nature. 1981 Jan 22;289(5795):298–300. [PubMed]
  • Wofsy D, Hardy RR, Seaman WE. The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on "helper" T cells that is involved in the response to class II major histocompatibility antigens. J Immunol. 1984 Jun;132(6):2686–2689. [PubMed]
  • Katagiri T, Tomiyama H, Kano K. Paul-Bunnell antigen in murine T cell differentiation: abnormal expression in MRL/Mp-lpr/lpr mice. J Immunol. 1986 Feb 1;136(3):913–919. [PubMed]
  • Melino MR, Dumont FJ, Habbersett RC, Hansen TH. Expression of a bone marrow-associated Ly-6 determinant on the T cell population expanding in the lymph nodes of the autoimmune mouse strain MRL/Mp-lpr/lpr. J Immunol. 1983 Apr;130(4):1843–1847. [PubMed]
  • Dumont FJ, Habbersett RC, Coker LZ, Nichols EA, Treffinger JA. High level expression of the plasma cell antigen PC.1 on the T-cell subset expanding in MRL/MpJ-lpr/lpr mice: detection with a xenogeneic monoclonal antibody and alloantisera. Cell Immunol. 1985 Dec;96(2):327–337. [PubMed]
  • Dumont FJ, Habbersett RC, Nichols EA. A new lymphocyte surface antigen defined by a monoclonal antibody (9F3) to the T cell population expanding in MRL/Mp-lpr/lpr mice. J Immunol. 1984 Aug;133(2):809–815. [PubMed]
  • Mountz JD, Mushinski JF, Mark GE, Steinberg AD. Oncogene expression in autoimmune mice. J Mol Cell Immunol. 1985;2(3):121–131. [PubMed]
  • Sheiness D, Gardinier M. Expression of a proto-oncogene (proto-myb) in hemopoietic tissues of mice. Mol Cell Biol. 1984 Jul;4(7):1206–1212. [PMC free article] [PubMed]
  • Davignon JL, Budd RC, Ceredig R, Piguet PF, MacDonald HR, Cerottini JC, Vassalli P, Izui S. Functional analysis of T cell subsets from mice bearing the lpr gene. J Immunol. 1985 Oct;135(4):2423–2428. [PubMed]
  • Katagiri K, Katagiri T, Eisenberg RA, Ting J, Cohen PL. Interleukin 2 responses of lpr and normal L3T4-/Lyt-2- T cells induced by TPA plus A23187. J Immunol. 1987 Jan 1;138(1):149–156. [PubMed]
  • Steinberg AD, Roths JB, Murphy ED, Steinberg RT, Raveche ES. Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/lpr mice. J Immunol. 1980 Aug;125(2):871–873. [PubMed]
  • Theofilopoulos AN, Balderas RS, Shawler DL, Lee S, Dixon FJ. Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice. J Exp Med. 1981 Jun 1;153(6):1405–1414. [PMC free article] [PubMed]
  • Smathers PA, Santoro TJ, Chused TM, Reeves JP, Steinberg AD. Studies of lymphoproliferation in MRL-lpr/lpr mice. J Immunol. 1984 Oct;133(4):1955–1961. [PubMed]
  • Fujiwara M, Kariyone A. One-way occurrence of graft-versus-host disease in bone marrow chimaeras between congenic MRL mice. Immunology. 1984 Oct;53(2):251–256. [PubMed]
  • Theofilopoulos AN, Balderas RS, Gozes Y, Aguado MT, Hang LM, Morrow PR, Dixon FJ. Association of lpr gene with graft-vs.-host disease-like syndrome. J Exp Med. 1985 Jul 1;162(1):1–18. [PMC free article] [PubMed]
  • Glasebrook AL, Sarmiento M, Loken MR, Dialynas DP, Quintans J, Eisenberg L, Lutz CT, Wilde D, Fitch FW. Murine T lymphocyte clones with distinct immunological functions. Immunol Rev. 1981;54:225–266. [PubMed]
  • Dialynas DP, Wilde DB, Marrack P, Pierres A, Wall KA, Havran W, Otten G, Loken MR, Pierres M, Kappler J, et al. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. [PubMed]
  • Sarmiento M, Glasebrook AL, Fitch FW. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed]
  • Budd RC, Schreyer M, Miescher GC, MacDonald HR. T cell lineages in the thymus of lpr/lpr mice. Evidence for parallel pathways of normal and abnormal T cell development. J Immunol. 1987 Oct 1;139(7):2200–2210. [PubMed]
  • Perkins DL, Michaelson J, Marshak-Rothstein A. The lpr gene is associated with resistance to engraftment by lymphoid but not erythroid stem cells from normal mice. J Immunol. 1987 Jan 15;138(2):466–469. [PubMed]
  • Cronin PS, Sing AP, Glimcher LH, Kelley VE, Reinisch CL. The isolation and functional characterization of autoimmune clones expressing inappropriate Ia. J Immunol. 1984 Aug;133(2):822–829. [PubMed]
  • Kelley VE, Farber NM, Williams JM, Strom TB. Inability of autoimmune mice with the lpr gene to spontaneously produce interleukin 3. Eur J Immunol. 1986 Apr;16(4):464–467. [PubMed]
  • Chandy KG, DeCoursey TE, Fischbach M, Talal N, Cahalan MD, Gupta S. Altered K+ channel expression in abnormal T lymphocytes from mice with the lpr gene mutation. Science. 1986 Sep 12;233(4769):1197–1200. [PubMed]
  • Katagiri T, Mori T, Nakano T, Ueno K, Kano K. Aberrant expression of Forssman and Paul-Bunnell antigens on lymph node cells of MRL/Mp-lpr/lpr mice. J Immunol. 1984 Dec;133(6):3143–3148. [PubMed]
  • Samelson LE, Davidson WF, Morse HC, 3rd, Klausner RD. Abnormal tyrosine phosphorylation on T-cell receptor in lymphoproliferative disorders. Nature. 1986 Dec 18;324(6098):674–676. [PubMed]

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