Cyclosporin A mediated immunosuppression <i>in vitro</i>: effect on high affinity interleukin‐2 receptor expression and ‐turnover

Jv, Povlsen; Bk, Møller; Bs, Christiansen; Cm, Petersen

doi:10.1111/j.1399-0039.1989.tb01671.x

Cited by 10 publications

(2 citation statements)

References 26 publications

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“…We treated chickens with CsA before exposure to IBDV. CsA has been known to selectively suppress T-cell function by inhibiting expression of IL-2 receptor and by blocking IL-2-mediated signal transduction (19,33,44). In our study, CsA treatment caused a detectable T-cell deficiency in chickens.…”

Section: Discussionmentioning

confidence: 59%

Characteristics of Bursal T Lymphocytes Induced by Infectious Bursal Disease Virus

Kim¹,

You

Kim

et al. 2000

J Virol

119

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Infectious bursal disease virus (IBDV) is an avian lymphotropic virus that causes immunosuppression.When specific-pathogen-free chickens were exposed to a pathogenic strain of IBDV (IM), the virus rapidly destroyed B cells in the bursa of Fabricius. Extensive viral replication was accompanied by an infiltration of T cells in the bursa. We studied the characteristics of intrabursal T lymphocytes in IBDV-infected chickens and examined whether T cells were involved in virus clearance. Flow cytometric analysis of single-cell suspensions of the bursal tissue revealed that T cells were first detectable at 4 days postinoculation (p.i.). At 7 days p.i., 65% of bursal cells were T cells and 7% were B cells. After virus infection, the numbers of bursal T cells expressing activation markers Ia and CD25 were significantly increased (P < 0.03). In addition, IBDV-induced bursal T cells produced elevated levels of interleukin-6-like factor and nitric oxide-inducing factor in vitro. Spleen and bursal cells of IBDV-infected chickens had upregulated gamma interferon gene expression in comparison with virus-free chickens. In IBDV-infected chickens, bursal T cells proliferated in vitro upon stimulation with purified IBDV in a dose-dependent manner (P < 0.02), whereas virus-specific T-cell expansion was not detected in the spleen. Cyclosporin A treatment, which reduced the number of circulating T cells and compromised T-cell mitogenesis, increased viral burden in the bursae of IBDV-infected chickens. The results suggest that intrabursal T cells and T-cell-mediated responses may be important in viral clearance and promoting recovery from infection.Infectious bursal disease virus (IBDV), an avian B-lymphotropic virus, causes an acute productive infection in actively dividing immunoglobulin M-expressing (IgM ϩ ) B cells (16,28). The bursa is the principal reservoir of virus replication, and peak virus titers in the bursa can be detected between 3 to 5 days after IBDV infection (20,38). The bursa of Fabricius is a unique, primary lymphoid organ in avian species, where B lymphocytes maturate and differentiate (14). The bursal follicles consist of B lymphocytes (85 to 95%), T cells (Ͻ4%), and other nonlymphoid cells (4,10,21,31). In the bursae of chickens infected with IBDV, productive viral replication is often associated with necrosis, apoptosis of lymphoid cells, inflammatory change, atrophy, and hemorrhages (16,25,38,42). Chickens infected with IBDV experience suppression in both humoral (8,13,32,39) and cellular (5, 23, 32) immunity. Humoral immunosuppression appears to be associated with IBDV-induced B-cell destruction, while the mechanism of cellular immunosuppression is largely elusive.Because viral replication is self-limiting, birds recover from the pathogenic effects of the virus. After the acute phase of the infection subsides, the bursal follicles become repopulated with B cells and immune competence is reestablished (24). The mechanisms that limit virus replication and promote recovery are not known and may involve virus-spe...

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Section: Discussionmentioning

confidence: 59%

Characteristics of Bursal T Lymphocytes Induced by Infectious Bursal Disease Virus

Kim¹,

You

Kim

et al. 2000

J Virol

119

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“…The ability of cyclosporin to interfere with the expression of low and high affinity IL-2R on stimulated T cells remains controversial (Bloemena et al 1988;Povlsen et al 1989;Reed et al 1986). Although cyclosporin inhibits IL-2 production, it has little effect on the expression of surface membrane IL-2R (Povlsen et al 1989).…”

Section: Il-2 Receptors (Il-2r)mentioning

confidence: 99%

Pharmacodynamic Monitoring of Cyclosporin

Awni

1992

Clinical Pharmacokinetics

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The efficacy of cyclosporin as an immunosuppressive agent is largely based on clinical indicators such as graft survival, rejection or nephrotoxicity. Therapeutic monitoring is necessary to evaluate the efficacy of cyclosporin therapy. The most widely used method for monitoring cyclosporin therapy is the measurement of predose through blood concentrations of the drug. The relationship of a single or multiple blood cyclosporin concentration to slowly evolving outcomes is difficult to establish. Some investigators have found a good correlation between cyclosporin trough concentrations on the one hand and cyclosporin toxicity and rejection on the other, but others have not. Therapeutic monitoring of cyclosporin may be enhanced using some biological assays for immunosuppression (pharmacodynamic monitoring) in addition to cyclosporin trough concentrations (pharmacokinetic monitoring). However, direct monitoring of the immune response to cyclosporin therapy using a clinically applicable biological assay is difficult. Some pharmacodynamic parameters have been suggested as biological markers in the clinical monitoring of cyclosporin.

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The cyclosporins

Řeháček

1995

Folia Microbiol

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This review presents the progress and some aspects achieved during recent years with cyclosporin sources, chemistry, biological activities, side effects, biosynthesis and metabolism. Although incomplete the results indicate future research trends and some white spots to be studied in the near future to afford unique insights into cell biology and to improve the search for similar and even more specific agents based on rational drug design.

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Cyclosporin A mediated immunosuppression in vitro: effect on high affinity interleukin‐2 receptor expression and ‐turnover

Cited by 10 publications

References 26 publications

Characteristics of Bursal T Lymphocytes Induced by Infectious Bursal Disease Virus

Characteristics of Bursal T Lymphocytes Induced by Infectious Bursal Disease Virus

Pharmacodynamic Monitoring of Cyclosporin

The cyclosporins

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