Rapamycine is as effective as costimulatory blockade on promoting the induction of fully MHC-mismatched mixed chimerism under irradiation free conditions.

, Sözen M. H.

American Transplant Congress 2001, Michigan, Amerika Birleşik Devletleri, 02 Mart 2001, cilt.1, sa.1, ss.248

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 1
  • Basıldığı Şehir: Michigan
  • Basıldığı Ülke: Amerika Birleşik Devletleri
  • Sayfa Sayıları: ss.248
  • Gazi Üniversitesi Adresli: Hayır

Özet

Induction of mixed chimerim (MC) is the most consistently successful approach to achieve transplantation tolerance. However, toxicity of irradiation as a preconditioning therapy has limited its clinical application. In thi\ study. we inveqtigated whether a high level of MC can he induced by irradiation-free approaches after infusion of a modest dose of bone marrow (BM) in a fully MHC-mimatched mouse combination and compared the capacity of rapamycin and T-cell costimulatory blockade (anti-CD40L mAb and CTLA4lg) on promoting BM engraftment, Donor-yxcific transfu\ion (0 25 ml) was given at day -7. ALS (0.3ml) wa\ administered I p. at day -8 and day -S. Buwlfan (Bu. 20 mglkg) and cyclophosphamide (Cy, 100 mag) were given i.p. at day -3 and days -2 Balb/c (H-2J) BM cells at a dose of 4x lo' were injected I.V. into each C57BL/6 mouIe (H2h) at day 0. Anti-CD40L (MRI. 0.5 mg) was given i.p. at days 0 and 2. and CTLA4lg (0.5 mg) way given i.p. at day 2. Rapamycin (Rapa) was administered orally at 2 mgfkg/d from day -I to day 2, then I mgjkgjd once every two day\ until day 14. The percentage of Balb/c donor-origin cells was determined by flow cytometry at 2, 4, 6 and X weeks post-BMT. The results of different group\ were as follows: Cclh Pe'rrcmtrpc "f Ik,"", nutty, ALS MRI.CTLA4tglapa S/1.62S'x Vl.hhm'k 1/5,7St5Y Busy. ALS MR I Rip V6.27i71 (~5.4lK3'8 h/h.UMS( nU+Cy..us MRI S/h,7*5* S/h.i1K7('r 4m.i7ii2TI( Bu+Cy.ALS RW wM.7~i(rx h/h.7w+im Bu*cy. ALS MRI.CILA4ig W6fPi7'2 4mYit1rX B"+CY. ALS c7LA41g %.!+i7'k 1/h,lYit 1% Busy MRI.TTU\~I~R~~~ 116.12'~ in, 17.2 ALS MRl.rTLA4lpRap I& lVh Our studies demonstrate that *table and high level of MC can be induced in a fully MHC-mismatched mouse combination after transplantation of a single modest dose of BM cells without irradiation. Rapa is as cffcctivc as T-cell cohnulatory blockade on promoting induction of MC across a complete MHC barrier without evidence of GVHD. Cmdilinning Thenpy Pos-Trmvptm# Trealmcnt