|
|
Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-04-1093.
 Previous Article | Table of Contents | Next Article 
Blood, 15 February 2003, Vol. 101, No. 4, pp. 1422-1429
IMMUNOBIOLOGY
Differential CD52 expression by distinct myeloid dendritic cell
subsets: implications for alemtuzumab activity at the level of antigen
presentation in allogeneic graft-host interactions in
transplantation
Gudrun Ratzinger,
John L. Reagan,
Glenn Heller,
Klaus J. Busam, and
James W. Young
From the Laboratory of Cellular Immunobiology,
Department of Medicine; Department of Epidemiology and Biostatistics;
Surgical Pathology Service, Department of Pathology; Allogeneic
Transplantation and Clinical Immunology Services, Division of
Hematologic Oncology, Department of Medicine; Memorial Sloan-Kettering
Cancer Center, New York, NY; and Weill Medical College of Cornell
University, New York, NY.
Alemtuzumab (anti-CD52; Campath 1-H) depletes both host and donor T
cells when used in preparative regimens for allogeneic transplantation.
This promotes engraftment even after nonmyeloablative conditioning and
limits graft-versus-host disease (GVHD) even after unrelated or major
histocompatibility complex (MHC) disparate allografts. We asked whether
anti-CD52 differentially targets antigen-presenting cells (APCs), in
addition to depleting T cells. Monocyte-derived dendritic cells (moDCs)
expressed abundant CD52 as expected. Langerhans cells (LCs) and
dermal-interstitial DCs (DDC-IDCs), however, never expressed CD52.
Immunostaining of skin and gut confirmed the absence of CD52 on these
resident DC populations under both steady-state and inflammatory
conditions. Although anti-CD52 functions primarily by
antibody-dependent cellular cytotoxicity (ADCC) in vivo, assessment of
its activity in vitro included complement-dependent lysis of
CD52+ cells. Anti-CD52 did not impair DC-T-cell adhesion,
diminish DC-stimulated T-cell proliferation, or alter moDC development in vitro. We propose that anti-CD52 abrogates GVHD not only by T-cell
depletion, but also by removing moDCs and their precursors. This would
mitigate moDC phagocytosis and presentation of host-derived antigens to
donor T cells in the inflammatory peritransplantation environment,
thereby limiting GVHD. The sparing of LCs and DDC-IDCs by anti-CD52, as
well as the recovery of donor-derived moDCs in a less inflammatory
environment later after transplantation, may allow all these DCs to
exert formative roles in graft-versus-tumor (GVT) reactions and immune
reconstitution. Whether these results support a separation of
deleterious from beneficial graft-host interactions at the level of
antigen presentation, rather than solely at the level of T cells, will
require further evaluation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Lapalombella, X. Zhao, G. Triantafillou, B. Yu, Y. Jin, G. Lozanski, C. Cheney, N. Heerema, D. Jarjoura, A. Lehman, et al.
A Novel Raji-Burkitt's Lymphoma Model for Preclinical and Mechanistic Evaluation of CD52-Targeted Immunotherapeutic Agents
Clin. Cancer Res.,
January 15, 2008;
14(2):
569 - 578.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Chakraverty and M. Sykes
The role of antigen-presenting cells in triggering graft-versus-host disease and graft-versus-leukemia
Blood,
July 1, 2007;
110(1):
9 - 17.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Loh, Y. Oyama, L. Statkute, K. Quigley, K. Yaung, E. Gonda, W. Barr, B. Jovanovic, R. Craig, D. Stefoski, et al.
Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used
Blood,
March 15, 2007;
109(6):
2643 - 2548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Zhang, S. K. Malek, T. M. Blasick, J. R. Pennington, K. K. Masker, M. Lun, and S. Potdar
C4d Positivity Is Often Associated with Acute Cellular Rejection in Renal Transplant Biopsies Following Campath-1H (Alemtuzumab) Induction
Ann. Clin. Lab. Sci.,
January 1, 2007;
37(2):
121 - 126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Zhang, J. R. Pennington, J. W. Prichard, T. M. Blasick, A. M. Brown, and S. Potdar
CD52 Antigen May Be a Therapeutic Target for Eosinophilic Rhinosinusitis
Ann. Clin. Lab. Sci.,
January 1, 2007;
37(2):
148 - 151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Meyer, C. M. Britten, D. Wehler, K. Bender, G. Hess, A. Konur, U. F. Hartwig, T. C. Wehler, A. J. Ullmann, C. Gentilini, et al.
Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation
Blood,
January 1, 2007;
109(1):
374 - 382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Collin, D. N.J. Hart, G. H. Jackson, G. Cook, J. Cavet, S. Mackinnon, P. G. Middleton, and A. M. Dickinson
The fate of human Langerhans cells in hematopoietic stem cell transplantation
J. Exp. Med.,
January 23, 2006;
203(1):
27 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Dao, M. Gomez-Nunez, C. Antczak, B. Kappel, J. Singh Jaggi, T. Korontsvit, V. Zakhaleva, and D. A. Scheinberg
Natural Killer Cells License Dendritic Cell Cross-Presentation of B Lymphoma Cell-Associated Antigens
Clin. Cancer Res.,
December 15, 2005;
11(24):
8763 - 8772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rossi and J. W. Young
Human Dendritic Cells: Potent Antigen-Presenting Cells at the Crossroads of Innate and Adaptive Immunity
J. Immunol.,
August 1, 2005;
175(3):
1373 - 1381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Crawley, M. Lalancette, R. Szydlo, M. Gilleece, K. Peggs, S. Mackinnon, G. Juliusson, L. Ahlberg, A. Nagler, A. Shimoni, et al.
Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT
Blood,
June 1, 2005;
105(11):
4532 - 4539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Ratzinger, J. Baggers, M. A. de Cos, J. Yuan, T. Dao, J. L. Reagan, C. Munz, G. Heller, and J. W. Young
Mature Human Langerhans Cells Derived from CD34+ Hematopoietic Progenitors Stimulate Greater Cytolytic T Lymphocyte Activity in the Absence of Bioactive IL-12p70, by Either Single Peptide Presentation or Cross-Priming, Than Do Dermal-Interstitial or Monocyte-Derived Dendritic Cells
J. Immunol.,
August 15, 2004;
173(4):
2780 - 2791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. F. Fagnoni, B. Oliviero, G. Giorgiani, P. De Stefano, A. Deho, C. Zibera, N. Gibelli, R. Maccario, G. Da Prada, M. Zecca, et al.
Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation
Blood,
July 1, 2004;
104(1):
281 - 289.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Zhang, S. K. Malek, J. W. Prichard, F. Lin, T. M Yahya, M. S. Schwartzman, R. P. Latsha, M. Skaletsky, E. R. Norfolk, R. E. Brown, et al.
Monocyte-Mediated Acute Renal Rejection after Combined Treatment with Preoperative Campath-1H (Alemtuzumab) and Postoperative Immunosuppression
Ann. Clin. Lab. Sci.,
April 1, 2004;
34(2):
209 - 213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Thomson, S. Ings, M. Watts, S. Mackinnon, and K. S. Peggs
CD34+ cell dose and the occurrence of GVHD in the presence of in vivo T-cell depletion
Blood,
January 15, 2004;
103(2):
743 - 743.
[Full Text]
[PDF]
|
|
|
|
|
