These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: alpha/beta-T cell receptor-directed therapy in rat allograft recipients. Long-term survival of cardiac allografts after pretreatment with R73 mAb is associated with upregulation of Th2-type cytokines.
    Author: Heidecke CD, Hancock WW, Westerholt S, Sewczik T, Jakobs F, Zantl N, Varzaru A, Siegling A, Kurrle R, Deusch K, Volk HD, Kupiec-Weglinski JW.
    Journal: Transplantation; 1996 Mar 27; 61(6):948-56. PubMed ID: 8623165.
    Abstract:
    Rejection of vascularized allografts still poses the major problem in organ transplantation. Therefore, transplant rejection of cardiac allografts was investigated in a rat model (BN-to-LEW) under alpha/beta-TCR (R73) mAb-targeted therapy. Two protocols were studied: posttransplant ("immunosuppressive") and pretransplant conditioning therapy. In posttransplant therapy over a wide dose range, R73 mAb only marginally improved cardiac allograft survival (7.8 +/- 0.8 days vs. 12.5 +/- 0.8 days at 0.1 mg/kg for 7 days). In contrast, conditioning treatment with low-dose (0.1 mg/kg) anti-alpha/beta-TCR mAb given 3 to 7 days prior to organ transplantation was highly effective and resulted in 50% permanent acceptance of cardiac allografts. R73 mAb-treated rats were monitored with respect to peripheral lymphocyte populations and intragraft cytokine levels. A temporary, incomplete reduction (CD5+ cells) and partial modulation (alpha/beta-TCR/CD5 double+ cells) in the peripheral blood was observed. In contrast to untreated controls, intragraft production of IL-2 and IFN-gamma at the mRNA and protein level was abolished in both post- and pretreated recipients. Interestingly, pretransplant mAb application was associated with augmented in situ elaboration of the Th2-type cytokines, IL-4 and IL-10, together with up-regulated TGF-beta and PGE. Increased expression of IL-4 and IL-10 continued to be observed in long-term surviving allografts. In conclusion, the mechanism of conditioning therapy with alpha/beta-TCR mAb prior to alloantigen exposure appears to be a switch from Th1 to Th2 response allowing long-term acceptance of allogeneic grafts.
    [Abstract] [Full Text] [Related] [New Search]