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Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin.

Publication ,  Journal Article
Kirk, AD; Mannon, RB; Kleiner, DE; Swanson, JS; Kampen, RL; Cendales, LK; Elster, EA; Wakefield, T; Chamberlain, C; Hoffmann, SC; Hale, DA
Published in: Transplantation
October 27, 2005

BACKGROUND: Perioperative lymphocyte depletion induces allograft tolerance in some animal models, but in humans has only been shown to reduce immunosuppressive requirements. Without maintenance immunosuppression, depleted human renal allograft recipients experience rejection characterized by infiltration of the allograft with monocytes and macrophages. T-cell depletion combined with a brief course of deoxyspergualin (DSG), a drug with inhibitory effects on monocytes and macrophages, induces tolerance in nonhuman primates. We therefore performed a trial to determine if lymphocyte depletion with alemtuzumab combined with DSG would induce tolerance in humans. METHODS: Five recipients of live donor kidneys were treated perioperatively with alemtuzumab and DSG and followed postoperatively without maintenance immunosuppression. Patients were evaluated clinically, by flow cytometry, and by protocol biopsies analyzed immunohistochemically and with real-time polymerase chain reaction. Results were compared to previously studied patients receiving alemtuzumab alone or standard immunosuppression. RESULTS: Despite profound T-cell depletion and therapeutic DSG dosing, all alemtuzumab/DSG patients developed reversible rejection that was similar in timing, histology, and transcriptional profile to that seen in patients treated with alemtuzumab alone. Chemokine expression was marked prior to and during rejections. CONCLUSIONS: We conclude that treatment with alemtuzumab and DSG does not induce tolerance in humans. Chemokine production may not be adequately suppressed using this approach.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

October 27, 2005

Volume

80

Issue

8

Start / End Page

1051 / 1059

Location

United States

Related Subject Headings

  • Transplantation Tolerance
  • Transcription, Genetic
  • T-Lymphocytes
  • Surgery
  • Middle Aged
  • Male
  • Lymphocyte Depletion
  • Lymphocyte Count
  • Lymph Nodes
  • Kidney Transplantation
 

Citation

APA
Chicago
ICMJE
MLA
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Kirk, A. D., Mannon, R. B., Kleiner, D. E., Swanson, J. S., Kampen, R. L., Cendales, L. K., … Hale, D. A. (2005). Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation, 80(8), 1051–1059. https://doi.org/10.1097/01.tp.0000174341.49741.8f
Kirk, Allan D., Roslyn B. Mannon, David E. Kleiner, John S. Swanson, Robert L. Kampen, Linda K. Cendales, Eric A. Elster, et al. “Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin.Transplantation 80, no. 8 (October 27, 2005): 1051–59. https://doi.org/10.1097/01.tp.0000174341.49741.8f.
Kirk AD, Mannon RB, Kleiner DE, Swanson JS, Kampen RL, Cendales LK, et al. Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation. 2005 Oct 27;80(8):1051–9.
Kirk, Allan D., et al. “Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin.Transplantation, vol. 80, no. 8, Oct. 2005, pp. 1051–59. Pubmed, doi:10.1097/01.tp.0000174341.49741.8f.
Kirk AD, Mannon RB, Kleiner DE, Swanson JS, Kampen RL, Cendales LK, Elster EA, Wakefield T, Chamberlain C, Hoffmann SC, Hale DA. Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation. 2005 Oct 27;80(8):1051–1059.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

October 27, 2005

Volume

80

Issue

8

Start / End Page

1051 / 1059

Location

United States

Related Subject Headings

  • Transplantation Tolerance
  • Transcription, Genetic
  • T-Lymphocytes
  • Surgery
  • Middle Aged
  • Male
  • Lymphocyte Depletion
  • Lymphocyte Count
  • Lymph Nodes
  • Kidney Transplantation