Reversible Suppression of Allo-Antibody Production by Cyclosporin A

Denham, S.; Styles, J M; Barfoot, Rita; Dean, Christopher

doi:10.1159/000232548

Cited by 13 publications

(11 citation statements)

References 13 publications

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“…However, the reduced effectiveness when the drug was administered 3 days before the implant, and the lack of effect when given on Day -7, indicate that it probably persists systemically little longer than 3 days. It has been shown also that animals receiving continuous daily doses of Cy A recovered rapidly from the effects once treatment was terminated (Denham et al, 1980 (1) Doses similar to those used in this study have been shown to permit the L survival of skin allografts in our rat LN LN colony (Denham et al, 1980). (2) Production of specific antibody to tumour antigens estimated by a direct binding assay was totally inhibited, as l,N+L described previously in athymic animals L (Eccles et al, 1979).…”

Section: Methodssupporting

confidence: 60%

“…Its mode of action is still imperfectly understood, but in contrast to other immunosuppressive or cytostatic drugs it has little effect on haemopoietic tissues and seems preferentially to inhibit T lymphocytes at an early stage of mitogenic triggering (Borel et al, 1978). Further advantages are that its effects seem to be reversed fairly rapidly, at least in some systems (Denham et al, 1980) and do not seriously compromise immunity to common pathogens.…”

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confidence: 99%

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Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumours

Eccles¹,

Heckford²,

Alexander³

1980

Br J Cancer

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Summary.-Cyclosporin A (Cy A), a novel immunosuppressive agent with apparently selective inhibitory effects on T lymphocytes and little myelotoxicity, was tested for its effects on a variety of syngeneic animal tumours including sarcomas, carcinomas and a T-cell lymphoma. Cy A, given orally or parenterally in repeated doses, had no effect on the growth rates of any of the tumours tested, but a highly significant effect on metastasis was seen in many cases. All the sarcomas examined in both rats and mice, and also the lymphoma, showed a marked increase in their metastases, in some cases even when administration of Cy A was delayed until after excision of the "primary" tumour implants. In contrast no effect of Cy A on metastasis was observed in animals bearing poorly immunogenic mammary or squamous-cell carcinomas. The metastases developing in Cy A-treated animals, when transplanted into normal syngeneic animals, showed no evidence of enhanced metastatic potential compared with their"parent" tumours.

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Section: Methodssupporting

confidence: 60%

mentioning

confidence: 99%

Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumours

Eccles¹,

Heckford²,

Alexander³

1980

Br J Cancer

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“…Control mice received similar daily treatments of olive oil. CsA treatment at 75 mg/kg/day, a dose shown to be immunosuppressive (Denham et al, 1980), reduced the DTH response in all strains at both day 4 and 10 p.i. to background levels comparable with responses of control uninfected mice.…”

Section: Short Communicationmentioning

confidence: 93%

The Effect of Cyclosporin on Major Histocompatibility Complex-linked Resistance to Murine Cytomegalovirus

Lawson

Hodgkin

Shellam

1989

Journal of General Virology

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SUMMARYThe ability of mice to survive infection with murine cytomegalovirus (MCMV) is known to be influenced by genes of the major histocompatibility complex (MHC). One hypothesis to account for this association is that MHC-linked resistance to MCMV is an 'immune response' gene effect, caused by differences in the strength of the MHCrestricted T cell response of mouse strains with different MHC haplotypes. Therefore, removal of T cell responses in mouse strains differing only at the MHC should render them equally susceptible to the virus infection. To test this hypothesis, the immunosuppressive drug cyclosporin (CsA) was used to reduce T cell responses in inbred congenic mouse strains carrying either a resistant or susceptible MHC haplotype. CsA reduced the delayed-type hypersensitivity (DTH) response to MCMV in both resistant and susceptible mouse strains to background levels, equivalent to control uninfected mice. CsA treatment had little effect on the susceptibility of C57BL/I 0 and B 10. B R mice to the virus and the differences in susceptibility between these strains remained. In contrast, CsA increased the susceptibility of the genetically susceptible BALB/c mice (H-2 d) by 100-fold and increased the susceptibility of resistant BALB.K mice (H-2 k) by 15-fold. Thus the H-2-determined difference in susceptibility between these strains was increased after CsA treatment. The results obtained with congenic strains show that MHC-linked resistance patterns to MCMV are not eliminated by CsA and suggest therefore that T cells are not responsible for this phenomenon. Interestingly, the mean time to death was delayed for CsA-treated BALB/c mice compared with untreated mice given equivalent virus doses. In addition, although CsA prevented DTH responses in both genetically susceptible A/J (H-2 a) and resistant CBA (H-2 k) mice, CsA treatment markedly increased the susceptibility of A/J mice (32-fold) but had little effect on the susceptibility of CBA mice to the virus.

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“…On human monocytes, mouse peritoneal MQ, rat spleen and activated peritoneal MQ, the FcyRI is unique in its ability to bind monomeric IgG with high affinity [3,6,8,201. The binding of monomeric IgG is subclass specific; in rats, only monomeric IgGZb, a major component of the plasma of normal adult rats (Peppard, cited in [20]), binds to the FcyRI. The physiological role of FcyRI-dependent binding of monomeric IgG2b in vivo remains to be determined.…”

Section: Properties Of the Fcyr For Monomeric Rat Iggb On Rat Bmm@mentioning

confidence: 99%

Binding of monomeric immunoglobulins by bone marrow‐derived mononuclear phagocytes; its modulation by interferon‐γ

Keller

Keist

Bazin³

et al. 1990

Eur J Immunol

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The ability of resting and activated rat bone marrow-derived mononuclear phagocytes (BMM phi) to bind monomeric rat, mouse, and human IgG was determined by means of flow cytometry. Rat IgG2b bound with high affinity (Kd approximately equal to 3 x 10(-9) M); binding was optimal at 4 degrees C and was only little affected by trypsin treatment. The other IgG bound with only low affinity (rat IgG2a, mouse and human IgG) or not at all to rat BMM phi (rat IgG1, rat IgG2c). The binding of rat IgG2b was not affected by the presence of a surplus of low-affinity binding IgG, and vice versa, indicating that high- and low-affinity IgG bind to different sites. Binding of high- and low-affinity IgG as well as expression of MHC class II molecules and of tumoricidal activity by BMM phi was markedly enhanced by rat interferon-gamma in low concentration (0.1 to 1.0 IU IFN-gamma/ml). On the other hand, heat-killed Corynebacterium parvum organisms, that were equally potent in triggering tumoricidal activity, neither enhanced the binding of IgG nor the expression of MHC class II molecules by BMM phi, suggesting that these abilities are not necessarily closely related phenomena.

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Reversible Suppression of Allo-Antibody Production by Cyclosporin A

Cited by 13 publications

References 13 publications

Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumours

Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumours

The Effect of Cyclosporin on Major Histocompatibility Complex-linked Resistance to Murine Cytomegalovirus

Binding of monomeric immunoglobulins by bone marrow‐derived mononuclear phagocytes; its modulation by interferon‐γ

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