Agonistic and Antagonistic Interactions of Anti-Interleukin 2 Receptor Monoclonal Antibodies in Rat Recipients of Cardiac Allografts

Kupiec‐Weglinski, Jerzy W.; Tilney, Nicholas L.; Stünkel, K; Grützmann, R.; Meide, P. H. Van Der; Stefano, Rossella Di; Diamantstein, Tibor

doi:10.1097/00007890-198901000-00004

Cited by 16 publications

(6 citation statements)

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“…Similar results have been recently reported in an allograft transplantation model. Administration of recombinant IFN-y reversed the prolongation of cardiac allograft survival in rats by an anti-rat IL2R mAb [13]. These results suggest that the T H 1 subset, via its product IFN-y , plays a physiological role in DTH induction and allograft rejection.…”

Section: Resultsmentioning

confidence: 72%

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4⁺ T_H1⁺ subset in mice

Diamantstein¹,

Eckert

Volk

et al. 1988

Eur J Immunol

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In mice, induction of delayed-type hypersensitivity (DTH) and of antibody formation to sheep red blood cells (SRBC) was inhibited by the anti-CD4 monoclonal antibody (mAb) GK1.5. However, anti-interleukin 2 mAb AMT-13 inhibited DTH response but not antibody formation. The inhibitory action of the mAb on DTH, but not an antibody formation, was reversed by concomitant injection of recombinant mouse interferon-gamma. These data provide the first in vivo evidence for the postulated physiological role of the CD4+ TH1 lymphocyte subset and indicate that the action of anti-interleukin 2 receptor mAb is restricted to this T helper subset.

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Section: Resultsmentioning

confidence: 72%

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4⁺ T_H1⁺ subset in mice

Diamantstein¹,

Eckert

Volk

et al. 1988

Eur J Immunol

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“…The in vivo effect of anti-IL-2R MAbs proved to be related to the recognition of different antigen determinants of the IL-2R molecule and the type of immunoglobulin subclass of the MAbs investigated (12,34). But in vitro assays on affinity parameters and epitope recognition, or the impact on in vitro cellular T-cell assays could not directly predict the effect of a given MAb in an in vivo transplantation situation (16).…”

Section: Discussionmentioning

confidence: 99%

Survival, function, morphology and serological aspects of rat renal allografts. Effect of short‐term treatment with cyclosporine A, anti‐CD4 and anti‐interleukin‐2 receptor monoclonal antibodies

Larsen

Kristensen

Starklint

et al. 1992

APMIS

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Survival, function, morphology and serological aspects of rat renal allografts. Effect of short-term treatment with cyclosporine A, anti-CD4 and anti-interleukin-2 receptor monoclonal antibodies. APMIS 100:The aim of this study was to investigate the effect of short-term treatment with cyclosporine A (CyA) combined with anti-CD4 (OX-38) and anti-interleukin-2 receptor (OX-39) monoclonal antibodies (MAbs) on graft survival, graft function, morphology, and anti-donor antibody levels in a BN-to-LEW rat kidney transplantation model. Spontaneous rejection occurred at 9.3 days (range 9-10 d). Administration of CyA (12.5 mg/kg/d) for 14 days prolonged graft survival to 33 days (range 2 3 4 0 d, P 100 d, P < 0.02 vs controls and CyA group). One of seven recipients had good graft function for more than 100 days. A three-fold increase of the MAb dosage did not improve mean graft survival (53.5 d), but three of eight recipients had well functioning grafts for > 100 days. Kidney function was characterized by reduced creatinine clearance, also in the recipients with long-term graft survival, and a defect in concentrating urine creatinine with subsequent pronounced increase in urinary output. Graft histology showed a complex pattern of interstitial alterations including mononuclear cell infiltration, fibrosis, tubular atrophy and vascular damage with intimal /endothelial cell hyperplasia and perivascular inflammation. In nine of 10 MAbtreated recipients with graft survival > 60 days, granular deposits of immunoglobulins and C3 were found by immunofluorescence microscopy (IFM). The deposits were localized in the glomerular capillaries and mesangium. IFM in MAb-treated control animals could not demonstrate any deposits. Flow cytometric evaluation of posttransplant serum samples against donor target cells showed increasing amounts of anti-donor antibodies until the time of rejection, while recipients with longterm graft function had moderately positive cross-matches up to two months after transplantation. Hereafter antibody titres decreased and cross-matches at the time of sacrifice were again negative. The morphological findings and the flow cytometric cross-match results seem to indicate a postponed antibody-mediated type of rejection. The reason why some kidney recipients showed decreasing antibody titres and stable long-term graft function is unclear.

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“…either by high dose CsA', or by the combined IL 2R-targeted therapy [25]. Thus, the essential feature of a positive effect of the latter therapeutic regiment seems to be the reduction of class I1 antigen-positive cells.…”

Section: Discussionmentioning

confidence: 99%

Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor‐targeted immunotherapy

Hahn

Gerdes²,

Lucke

et al. 1988

Eur J Immunol

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We investigated immunohistochemically the phenotypes of mononucleated cells invading pancreatic islets of diabetic BB/OK rats in comparison to the diabetes-resistant parental strain, and 12 and 120 days after a temporary treatment (10 days) with a monoclonal antibody (1 mg/kg b.w.) directed against interleukin 2 receptor (IL 2R) combined with a subtherapeutic dose of cyclosporin A (1.5 mg/kg b.w.). Using a panel of monoclonal antibodies (OX-19, OX-8, W3/25, KI-M2R, OX-6, OX-17, ART-18) and the alkaline phosphatase anti-alkaline phosphatase system to visualize the bound primary antibodies, we observed an even distribution of mononucleated cells across the endocrine pancreas at a "background" level when obtained from diabetes-resistant parental rat strain. Diabetic BB/OK rats, characterized by a moderate hyperglycemia and a marked decrease of pancreatic insulin content, displayed a remarkable accumulation of mononucleated cells in the endocrine pancreas. Morphometric studies revealed an increase of all phenotypes investigated, nearly all mononucleated cells expressed class II histocompatibility antigens (OX-6+, OX-17+) and the number of cells expressing the IL 2R (ART-18+) was markedly enhanced. Sixty-seven percent of the immunotherapeutically treated BB/OK rats normalized plasma glucose and enhanced pancreatic insulin content. The successfully treated animals are characterized by a decrease of cells invading pancreatic islets (OX-19+, OX-8+, W3/25+, KI-M2R+), a decrease of class II histocompatibility antigen and IL 2R expression. The number of IL 2R cells is also diminished in the endocrine pancreas of unsuccessfully treated BB rats.

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Agonistic and Antagonistic Interactions of Anti-Interleukin 2 Receptor Monoclonal Antibodies in Rat Recipients of Cardiac Allografts

Cited by 16 publications

References 0 publications

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4⁺ T_H1⁺ subset in mice

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4⁺ T_H1⁺ subset in mice

Survival, function, morphology and serological aspects of rat renal allografts. Effect of short‐term treatment with cyclosporine A, anti‐CD4 and anti‐interleukin‐2 receptor monoclonal antibodies

Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor‐targeted immunotherapy

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Agonistic and Antagonistic Interactions of Anti-Interleukin 2 Receptor Monoclonal Antibodies in Rat Recipients of Cardiac Allografts

Cited by 16 publications

References 0 publications

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4+ TH1+ subset in mice

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4+ TH1+ subset in mice

Survival, function, morphology and serological aspects of rat renal allografts. Effect of short‐term treatment with cyclosporine A, anti‐CD4 and anti‐interleukin‐2 receptor monoclonal antibodies

Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor‐targeted immunotherapy

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Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4⁺ T_H1⁺ subset in mice

Reversal by interferon‐γ of inhibition of delay ed‐type hypersensitivity induction by anti‐CD4 or antiinterleukin 2 receptor (CD25) monoclonal antibodies. Evidence for the physiological role of the CD4⁺ T_H1⁺ subset in mice