Contributed equally to this paper.
Guiding Postablative Lymphocyte Reconstitution as a Route Toward Transplantation Tolerance
Article first published online: 19 MAY 2014
© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 14, Issue 7, pages 1678–1689, July 2014
How to Cite
Piotti, G., Ma, J., Adams, E., Cobbold, S. and Waldmann, H. (2014), Guiding Postablative Lymphocyte Reconstitution as a Route Toward Transplantation Tolerance. American Journal of Transplantation, 14: 1678–1689. doi: 10.1111/ajt.12756
- Issue published online: 20 JUN 2014
- Article first published online: 19 MAY 2014
- Manuscript Accepted: 22 MAR 2014
- Manuscript Revised: 28 FEB 2014
- Manuscript Received: 9 MAY 2013
- ERC Framework Programme 7 “Betacell therapy”
- ERC Advanced Investigator Grant “PARIS”
- Medical Research Council
- Italian Society of Nephrology
Additional Supporting Information may be found in the online version of this article.
|ajt12756-sm-0001-SuppFig-S1.ppt||72K||Figure S1: Treatment with αIL-7R halts B cell development at an early stage. Bone marrow was collected from hCD52-Tg mice treated with PBS or αIL-7R and analyzed by FACS for the expression of B cell markers. The percentages of CD45R/220+ kappa- and kappa+ cells were reduced in mice treated with αIL-7R (0.4% vs 15.2%, and 0.2% vs 3.0%).|
|ajt12756-sm-0001-SuppFig-S2.ppt||108K||Figure S2: The combination of T- and B cell depletion does not promote long-term graft survival. (A) Spleen cells were collected from hCD52-Tg mice not treated (n = 3), treated with campath (n = 3), with αCD20 (n = 3), or with both drugs (n = 4) on day 7. Vital cells were counted and characterized by FACS. Shown are means ±SD of absolute numbers per spleen of CD3+ cells (white bars) and CD19+ cells (gray bars). Absolute numbers were calculated as product of numbers of spleen vital cells and percentage of CD3+ or CD19+ cells. (B) Fully mismatched B6 skin grafts were transplanted to hCD52-Tg mice under the cover of αCD20 alone (Δ, n = 6) or in combination with campath (□; n = 5). Lymphocyte antibody depletion could not prevent graft rejection in any mice; however treatment with αCD20 and campath significantly delayed rejection compared to αCD20 alone (MST 19 and 11 days, respectively, p = 0.0015).|
|ajt12756-sm-0001-SuppFig-S3.ppt||114K||Figure S3: Treatment with αIL-7R reduces the production of anti-donor MHC antibodies. Serum was collected from naïve hCD52-Tg mice (n; n = 2) or hCD52-Tg mice 3 weeks after the transplantation of B10 skin grafts under the cover of different treatments. Serum was then incubated with B10 thymocytes at progressive dilutions, and relative quantification of anti-donor MHC antibodies (mouse anti-mouse H-2b) was determined by FACS using a goat anti-mouse IgG as a secondary antibody. The level of anti-donor antibodies in mice treated with campath+αIL-7R, irrespective of graft acceptance (◦; n = 3) or rejection (Δ; n = 3), was lower than that in grafted mice treated with campath alone (□; n = 4) or with PBS (•; n = 2) (p < 0.0001 for both comparisons). No difference in antibody titers was found between mice treated with campath+αIL-7R with a viable graft (n = 3) compared to those that had rejected their graft (n = 3) (p > 0.05).|
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