Deoxyspergualin inhibits cytotoxic T lymphocytes but not NK or LAK cells

Kerr, Peter G.; Atkins, Robert C.

doi:10.1038/icb.1991.26

Cited by 12 publications

(4 citation statements)

References 23 publications

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“…It seems well established that DSG inhibits generation and differentiation of cytotoxic Tcells [14][15][16][17] and B cells including their production of antibodies [13,18,19], In spite of the striking in vivo effects of DSG on T helper cell-mediated autoimmune diseases, its putative influence on T helper lymphocytes has not unequivocally been clarified. Thus, inhibition of T cell proliferation or cytokine secretion has been reported by some [20][21][22], but more frequently been negated by others [14 16,19,23-25], According to the latter results it would become necessary to explain the beneficial effect of DSG on T helper cell-mediated autoimmune diseases by inhibition of other effector cells participating in the autoreactive immune attack. For example, effects of DSG on macrophages [4,5,26] have been described, but 49S it is unknown whether these effects are decisive for the therapeutic efficacy of DSG.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, inhibition of T cell proliferation or cytokine secretion has been reported by some [20][21][22], but more frequently been negated by others [14 16,19,23-25], According to the latter results it would become necessary to explain the beneficial effect of DSG on T helper cell-mediated autoimmune diseases by inhibition of other effector cells participating in the autoreactive immune attack. For example, effects of DSG on macrophages [4,5,26] have been described, but it is unknown whether these effects are decisive for the therapeutic efficacy of DSG.…”

Section: Introductionmentioning

confidence: 99%

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Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Jung

Toyka

Hartung

1994

Clinical and Experimental Immunology

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SUMMARYThe influence of the immunosuppressivc antibiotic agent 15-deoxyspergualin (DSG) on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo. DSG did not inhibit antigen-or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro. However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG, Like activationinduced T cell proliferation, IL-2-dependent growth of CD4^ T line cells was not affected by DSG, Preincubation of CD4^ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen-but not mitogen-induced activation of these T cells, although neither density of T eel) receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG. Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of DSG on CD4''' T lymphocytes, but not macrophages. It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of DSG on transplantation rejection and experimental autoimmune diseases, despite a normal mitogen response of T cells exposed to DSG in vivo and in vitro.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Jung

Toyka

Hartung

1994

Clinical and Experimental Immunology

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“…This operates at the level of cyto toxic T lymphocyte generation [45,46]. Suppression of cytotoxic T lymphocyte generation in vitro can be over come by the addition of interleukin 2 (IL-2) or interferon gamma [45,46].…”

Section: T Cellsmentioning

confidence: 99%

Deoxyspergualin: A New Immunosuppressive Drug for the Treatment of Auto-Immune Disease

Kerr

Lan

Tesch

et al. 1995

Nephron

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“…DSP has been shown to inhibit both primary and secondary antibod\ responses [11.14]. to inhibit primary and secondary cytotoxic l>mphocyte responses [15,16], and to suppress the development of T cell and macrophage infiltration during allograft rejection [11], In addition. DSP has been shown to reverse steroid-resistant acute rejection episodes [17.IS].…”

mentioning

confidence: 99%

Suppression of pulmonary injury in experimental ‘Goodpasture's syndrome’ by deoxyspergualin (DSP)

Lan

Zarama

Kerr

et al. 1994

Clinical and Experimental Immunology

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SUMMARY DSP is a potent immunosuppressive drug which can prevcnt allograft rejection and suppress acute rejection episodes. In this study, the ability of DSP to suppress pulmonary injury in experimental Goodpasture's syndrome was investigated. Passive accelerated anti‐glomerular basement membrane (GBM) disease was induced in rats by priming with rabbit IgG. followed 5 days later by injection of rabbit anti‐GBM serum (day 0). Groups of five animals were treated with DSP (5 mg/kg iniraperitoneally per day) or saline (untreated) from day 0 until being killed on days 1,7,14or21. At day I, both DSP‐treated and untreated animals exhibited similar pulmonary haemorrhage, oedema, and prominent perivascular leucocyte infiltration. Untreated animals subsequently developed severe widespread pulmonary damage including granulomatous lesions and extensive fibrosis, which correlated with infiltration of macrophages and immune‐activated (IL‐2R′) mononuelcar cells (P<0.01). Tumour necrosis factor‐alpha (TNF‐α), a known mediator of acute lung damage, was produced by pulmonary mononuclear cells throughout the experimental course. In contrast, DSP treatment resolved pulmonary haemorrhage, prevented the appearance of granulomatous lesions, and resulted in a histologically normal lung structure by day 21. This improvement was associated with a marked suppression of maerophage infiltration (P<0.001 versus untreated), accumulation of immune activated (IL‐2R′) mononuelear cells (P<0.05 versus untreated), and TNF‐α production (P<0.05 versus untreated). DSP treatment also suppressed the deposition of rat anti‐rabbit IgG immunoglobulin and C3 along the alveolar basement membrane (P<0.05 versus untreated). In conclusion, DSP suppressed pulmonary injury in accelerated anti‐GBM disease by acting on the local cellular immune response and the systemic humoral immune response. Further studies are warranted to determine whether this could be a useful drug for the treatment of Goodpasture's syndrome in humans.

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Deoxyspergualin inhibits cytotoxic T lymphocytes but not NK or LAK cells

Cited by 12 publications

References 23 publications

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Deoxyspergualin: A New Immunosuppressive Drug for the Treatment of Auto-Immune Disease

Suppression of pulmonary injury in experimental ‘Goodpasture's syndrome’ by deoxyspergualin (DSP)

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