In vitro depletion of tissue-derived dendritic cells by CMRF-44 antibody and alemtuzumab: implications for the control of Graft-versus-host disease.

Abstract:

:Graft-versus-host disease (GvHD), a life-threatening complication of bone marrow transplantation, is initiated by donor T cells reacting to recipient dendritic cells (DC). GvHD can be controlled by attenuating donor T cells, but few strategies exist to target DC, particularly resident tissue DC, despite recent evidence of their importance. In this report, CMRF-44, a mouse monoclonal IgM reactive to human DC, is tested against human Langerhans cells (LC) in vitro. CMRF-44 antigen is expressed at low level on fresh LC but is up-regulated 40-60-fold during migration. CMRF-44 and complement kill more than 97% of migratory LC in vitro and inhibit allostimulation by LC up to 95%. In comparison, alemtuzumab, which binds CD52, reacts weakly with primary LC and fails to induce significant lysis with complement (less than 5%). These results highlight the potential of new therapeutic antibodies active against tissue DC to control graft-versus-host reactions.

journal_name

Transplantation

journal_title

Transplantation

authors

Collin MP,Munster D,Clark G,Wang XN,Dickinson AM,Hart DN

doi

10.1097/01.tp.0000149321.86104.c4

subject

Has Abstract

pub_date

2005-03-27 00:00:00

pages

722-5

issue

6

eissn

0041-1337

issn

1534-6080

pii

00007890-200503270-00019

journal_volume

79

pub_type

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