Induction of Long-Term Survival of Rat Skin Allografts by a Novel, Highly Efficient Anti-Cd4 Monoclonal Antibody

Lehmann, Manfred; Sternkopf, Frank; Metz, Frauke; Brock, Josef; Döcke, W D; Plantikow, A.; Kuttler, Beate; Hahn, H.-J.; Ringel, Bruno; Volk, H. D.

doi:10.1097/00007890-199212000-00003

Cited by 39 publications

(17 citation statements)

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“…Simultaneous staining of lymphocytes with the non-depleting anti-CD4 mAb, RIB 5/2, and either of the depleting anti-CD4 mAbs, W3j25 or OX-35, results in the same fluorescenceactivated cell sorting (FACS) binding pattern as that observed with either single depleting mAb alone, thus indicating that all three antibodies detect the same molecule [29]. However, RIB 5/2 defines a different epitope of the CD4 molecule, since there is no competition with the binding of RIB 5/2 by W3/25 or OX-35 [12]. The IgG2a content of the ascites (12 mg/ml) was determined by ELISA [121.…”

Section: Monoclonal Antibodiesmentioning

confidence: 79%

“…RIB 5/2 mAb (IgG2a) was produced by the fusion of the mouse myeloma cells X63-Ag8.653 and splenocytes from mice immunized with concanavalin A-activated BDIX rat lymphocytes [12]. RIB 5/ 2 precipitates a 53-kDa polypeptide expressed on rat thymocytes and splenocytes.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

“…The ultimate goal in organ transplantation is the achievement of donor-specific unresponsiveness without this non-specific effect. The anti-rat non-depleting CD4 mAb, RIB 5/2, has been shown to modulate the CD4 glycoprotein without eliminating the CDCpositive T cells [12].…”

Section: Introductionmentioning

confidence: 99%

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Donor-specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft

Margenthaler

Otomo

et al. 2003

Transplant International

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This study examined whether a heart or kidney graft could provide protection for the more resistant skin graft. Buffalo rat recipients were given a single dose of RIB 5/2 (non-depleting anti-CD4 mAb) plus i.v. Lewis splenocytes 21 days before being given Lewis heart or kidney grafts. Lewis skin was grafted either simultaneously with, or after, long-term ( > 50 days) Lewis heart or kidney allograft acceptance. Immune responsiveness was analyzed by in vitro mixed lymphocyte culture (MLC), cytotoxic T lymphocytes (CTLs), and limiting dilution analysis (LDA). While i.v. alloantigen plus RIB 5/2 resulted in long-term acceptance of heart and kidney, survival of skin grafts alone was not prolonged. However, simultaneous transplantation with kidney, but not heart, resulted in long-term skin graft acceptance, while skin grafts subsequently grafted to recipients tolerant to kidney or heart were not accepted. In vitro analysis revealed a down-regulation of proliferation, cytotoxicity, and precursor T-helper cells (pThs)/precursor cytotoxic T lymphocytes (pCTLs) in Buffalo recipients accepting Lewis kidney and skin allografts. While RIB 5/2 plus Lewis splenocytes do not prolong the survival of skin grafts, Lewis skin grafted simultaneously with a kidney, but not heart, is accepted indefinitely and provides donor-specific protection for a subsequent skin graft.

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Section: Monoclonal Antibodiesmentioning

confidence: 79%

Section: Monoclonal Antibodiesmentioning

confidence: 99%

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Donor-specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft

Margenthaler

Otomo

et al. 2003

Transplant International

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“…For the induction of permanent graft acceptance rats were treated with the nondepleting anti-CD4mAb (RIB5/2) at a dose of 10mg/kg b.w./day intraperitoneally on Days À1 until þ3 as previously described (39)(40)(41)(42). Some recipients additionally received 10 mg/kg b.w./day CsA subcutaneously on Days 0-9.…”

Section: Kidney Transplantation and Immunosuppressive Treatmentmentioning

confidence: 99%

Mechanisms and Rescue Strategies of Calcineurin Inhibitor Mediated Tolerance Abrogation Induced by Anti-CD4 mAb Treatment

Siepert

Brösel

Vogt

et al. 2013

American Journal of Transplantation

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“…RIB5/2 (a nondepleting mouse anti-rat CD4 mAb) was purified from ascites by protein A affinity chromatography and the concentration was determined by enzyme-linked immunosorbent assay using IgG2a standards (Sigma, Deisenhofen, Germany) (14,15). FTY720 was kindly provided by Novartis Pharma GmbH, Nürnberg, Germany.…”

Section: Immunosuppressive Treatment and Kidney Transplantationmentioning

confidence: 99%

FTY720 Prevents Anti-CD4 mAb-Induced Tolerance but Cannot Reverse Established Tolerance in a Rat Kidney Transplantation Model

Schroeder

Risch

Kotsch

et al. 2004

American Journal of Transplantation

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FTY720 is highly effective in various models of transplantation and autoimmunity. In order to find drugs that act synergistically with a tolerance-inducing nondepleting anti-CD4 mAb we studied this combination in a strong DA to LEW kidney transplantation model. Rats were treated with 0.3 mg/kg of FTY720 for 14 days and anti-CD4 mAb RIB5/2, alone or in combination. After kidney transplantation serum creatinine and blood lymphocyte counts were monitored. Immunohistology, ELISPOT and TaqMan TM -PCR analysis of biopsies were performed.Short-term application of RIB5/2 but not FTY720 induced long-term survival of kidney transplants. Moreover, the combination of FTY720 + + RIB5/2 prevented tolerance induction. In the combination group serum creatinine levels increased 1 week after cessation of therapy and all rats died from uremia within 72 days. Intragraft immunohistology, ELISPOT and real-time RT-PCR analysis at day 21 demonstrated an enhanced T-cell infiltration and activation but a diminished upregulation of protective genes in the grafts from recipients receiving the combination therapy. In contrast, delayed application of FTY720 to RIB5/2-treated rats did not interact with RIB5/2-induced tolerance.In summary, FTY720 is powerful in preventing intragraft infiltration by naive T cells but this might also affect the early development of graft-protecting regulatory T cells and tolerance induction.

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Induction of Long-Term Survival of Rat Skin Allografts by a Novel, Highly Efficient Anti-Cd4 Monoclonal Antibody

Cited by 39 publications

References 0 publications

Donor-specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft

Donor-specific renal, but not cardiac, allograft tolerance promotes engraftment of the normally rejected rat skin graft

Mechanisms and Rescue Strategies of Calcineurin Inhibitor Mediated Tolerance Abrogation Induced by Anti-CD4 mAb Treatment

FTY720 Prevents Anti-CD4 mAb-Induced Tolerance but Cannot Reverse Established Tolerance in a Rat Kidney Transplantation Model

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