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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2586-2591
TRANSPLANTATION
Campath-1G causes rapid depletion of circulating host dendritic
cells (DCs) before allogeneic transplantation but does not delay donor
DC reconstitution
Phennapha Klangsinsirikul,
G. Ian Carter,
Jennifer L. Byrne,
Geoff Hale, and
Nigel H. Russell
From the Division of Haematology, School of Clinical
Laboratory Sciences, University of Nottingham, Nottingham, United
Kingdom, and the Sir William Dunn School of Pathology, University of
Oxford, Oxford, United Kingdom.
Graft-versus-host disease (GVHD), a major complication after
allogeneic transplantation, can be abrogated by the Campath (anti-CD52) monoclonal antibody. The induction of acute GVHD requires host antigens
to be presented to donor T cells by antigen-presenting cells (APCs).
Recent evidence has suggested that only host APCs can interact with
donor T cells in the induction of GVHD. Because CD52 has been reported
to be expressed on DCs, we reasoned that pretransplant Campath-1G might
have a direct effect on circulating DCs in addition to any effects on
donor T cells. Using direct immunostaining, we demonstrated expression
of CD52 on DCs and that Campath-1G killed purified DCs in
vitro. In vivo Campath also depleted DCs. Twenty-four hours after the
first dose of Campath-1G, circulating DCs were reduced by a mean of
79% (range, 44%-96%). By day 0 after 5 doses of Campath-1G and
chemoradiotherapy conditioning, DCs became undetectable in 7 of 9 cases, whereas in 6 of 7 patients receiving conditioning therapy
without Campath-1G, host DCs were still detectable. The reconstitution
of circulating DCs after transplantation was not affected by Campath-1G
and in both groups DC1 (CD11c+) recovered more rapidly than
DC2 (CD11c ). Analysis of chimerism confirmed that the DCs
recovering after transplantation in patients receiving Campath-1G were
of donor origin. We conclude that in vivo Campath-1G causes a rapid
depletion of host circulating DCs and that this may, in part, explain
the low incidence of acute GVHD. The reconstitution of donor DCs was not delayed, which may be important in preserving immune reconstitution.
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