Relative Inability to Induce Tolerance in Adult NZB and NZB/NZW F1 Mice

Staples, Parker J.; Talal, Norman

doi:10.1084/jem.129.1.123

Cited by 129 publications

(40 citation statements)

References 20 publications

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“…However, it is also possible that the loss of tolerance was due in part to underlying defects in the B/W strain. This possibility is consistent with previous studies indicating that B/W mice are relatively resistant to tolerance induction and that this resistance increases with age (64)(65)(66). It is unlikely that the loss of tolerance was due to progressive disease, since tolerance was broken simultaneously in both the anti-IL-6 and GL1 13 groups even though the GL1 13 group had evidence of SLE several months before the loss of tolerance to the rat mAb.…”

Section: Discussionsupporting

confidence: 80%

Interleukin 6 promotes murine lupus in NZB/NZW F1 mice.

Finck

Chan²,

Wofsy³

1994

J. Clin. Invest.

225

134

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To investigate the role of IL-6 in systemic lupus erythematosus (SLE), we selectively inhibited IL-6 in lupus-prone NZB/ NZW F1(B/W) mice by chronic administration of a rat mAb to mouse IL-6. Anti-IL-6 alone elicited an anti-rat response that blocked its biologic effects. To circumvent this problem, we rendered B/W mice tolerant to the rat mAb by administration of anti-CD4 concurrent with the first dose of anti-IL-6. Thereafter, the mice received weekly injections of anti-IL-6 alone. There were two control groups: one group received the tolerizing regimen of anti-CD4 along with a control rat IgG1 mAb (GL113) instead of anti-IL-6; the other control group received PBS. Mice that received anti-CD4 were tolerant to the rat mAb for 6 mo. Throughout this period, treatment with anti-IL-6 prevented production of anti-dsDNA, significantly reduced proteinuria, and prolonged life. Mice that received anti-IL-6 without anti-CD4 developed an immune response to the rat mAb and then developed anti-dsDNA antibodies, proteinuria, and mortality comparable with control mice. These findings establish that IL-6 promotes autoimmunity in B/W mice. They further indicate that, although mAb to IL-6 can suppress murine lupus, the development of host immunity to the mAb abrogates its beneficial effects. Finally, this is the first study to demonstrate that a brief course of anti-CD4 can induce tolerance to another therapeutic mAb, in this case an anticytokine mAb. (J. Clin. Invest. 1994. 94:585-591.)

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Section: Discussionsupporting

confidence: 80%

Interleukin 6 promotes murine lupus in NZB/NZW F1 mice.

Finck

Chan²,

Wofsy³

1994

J. Clin. Invest.

225

134

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“…The one striking difference between the NZB mice and other mouse strains is the development of autoimmune disease in the NZB strain, characterized by a number of abnormalities in both humoral and cellular immunity. Prominent among these is an increased resistance to tolerance induction (9). Expanded Tcell clones specific for minor H antigens may exist in the NZB already in vivo, so that the observed reaction of NZB against 1-1-2 identical target cells would constitute a secondary immune reaction against these antigens.…”

Section: Discussionmentioning

confidence: 99%

Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

Botzenhardt¹,

Klein²,

Ziff³

1978

The Journal of Experimental Medicine

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NZB mice develop a progressive autoimmune disease resembling human systemic lupus erythematosus (1-3) in many respects. The natural history of this disease is characterized by the development of hemolytic anemia, splenomegaly, glomerulonephritis, and numerous autoantibodies (4-5). Humoral immune responses to a number of antigens have been found to be abnormal in NZB mice (4-8) and induction of tolerance to soluble protein antigens to be more difficult in NZB than in other strains (9). A variety of mechanisms have been proposed for these abnormalities (10-14). In older mice, T-cell functions like mitogen responsiveness (15), graft-versus-host reactivity (16), and cell-mediated cytotoxicity (17-20) have generally been decreased, although in a recent report (21) the level of some of these functions in the NZB strain has been observed to be within the range of normal.In previous investigations (17-21) the phenomenon of cell-mediated lympholysis (CML) I in NZB mice has been examined by using targets differing at the major histocompatibility complex (MHC) from NZB or against virus-infected targets. In the experiments reported here, the primary in vitro CML activity of NZB mice was investigated against syngeneic targets and against targets carrying the NZB MHC type (H-2 d) on a background differing from NZB. In this situation primary in vitro CML activity is not generated by normal strains (22)(23)(24)(25)(26). In the present experiments a significant unidirectional CML was unexpectedly demonstrated against H-2 identical allogeneic targets by NZB effector cells. These results represent the first demonstration of a CML reaction in a primary in vitro system directed against unmodified targets which do not differ from the cytotoxic effectors in the MHC. They provide evidence for a qualitative difference in T-cell cytotoxic function between NZB mice and control

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“…In older animals, tighter connections resulting from immunological experience would be a hindrance to this plasticity. Mouse strains which display abnormal patterns of idiotypic connectivity when young are susceptible to autoimmune defects and tend to be refractory to oral tolerance induction (12,15,37,84). Aging is associated with a progressive decline in antibody responsiveness (see Figure 1) to foreign antigens, such as bacterial proteins, and SRBC, paralleled by a progressive rise in the production of self-reactive (auto) antibodies (67,86,87).…”

Section: Mechanisms Of Tolerance/aging and Idiotypic Connectivitymentioning

confidence: 99%

Aging and immunoglobulin isotype patterns in oral tolerance

Faria

Ficker

Speziali

et al. 1998

Braz J Med Biol Res

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In the present review we address oral tolerance as an important biological phenomenon and discuss how it is affected by aging. Other factors such as frequency of feeding and previous digestion of the antigen also seem to influence the establishment of oral tolerance. We also analyze immunoglobulin isotypes of specific antibodies formed by tolerant and immunized animals of different ages submitted to different conditions of oral antigen administration. Isotypic patterns were studied as a parameter for assessing the pathways of B and T cell interactions leading to antibody production.

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Relative Inability to Induce Tolerance in Adult NZB and NZB/NZW F1 Mice

Cited by 129 publications

References 20 publications

Interleukin 6 promotes murine lupus in NZB/NZW F1 mice.

Interleukin 6 promotes murine lupus in NZB/NZW F1 mice.

Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

Aging and immunoglobulin isotype patterns in oral tolerance

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