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M9630571.TXT
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1996-02-27
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Document 0571
DOCN M9630571
TI Chloroquine treatment affects T-cell priming to minor histocompatibility
antigens and graft-versus-host disease.
DT 9603
AU Schultz KR; Bader S; Paquet J; Li W; Department of Pediatrics,
University of British Columbia,; Vancouver, Canada.
SO Blood. 1995 Dec 1;86(11):4344-52. Unique Identifier : AIDSLINE
MED/96082193
AB Graft-versus-host disease (GVHD) caused by T-cell recognition of minor
histocompatibility (MiHC) antigens is a major complication of bone
marrow transplantation. GVHD therapy has focused on removal or
suppression of donor T cells, but modulation of MiHC antigen
presentation to CD4+ T cells may represent an alternative approach.
Chloroquine is known to inhibit major histocompatibility complex (MHC)
class II presentation of antigen in vitro by affecting invariant chain
dissociation from MHC class II. The goal of this study was to evaluate
the role of chloroquine in abrogating T-cell priming to MiHC and GVHD in
mice after transplantation of an MiHC incompatible donor. C57BL/6 mice
were treated with phosphate-buffered saline or chloroquine at 400
micrograms intraperitoneally every day for 5 days before priming with
BALB.B cells (MiHC-incompatible) followed by weekly injections of
chloroquine at 400 micrograms for 4 to 8 weeks. Chloroquine treatment
decreased the proliferative T-cell response to MiHC by 67% and the
cytolytic T-cell activation by greater than 50%. After bone marrow
transplantation (LP/J into C57BL/6; MiHC-incompatible), GVHD was
significantly decreased in chloroquine-treated mice (17% with GVHD) as
compared with that in controls (92% with GVHD). Chloroquine treatment
did not have other effects in vivo on the normal T- and B-cell mitogenic
responses, T-cell allogeneic responses, and MHC class II and I surface
expression. Chloroquine treatment does decrease the ability of C57BL/6
antigen-presenting cells to stimulate C3H.SW T cells reactive with MiHC
expressed on C57BL/6 cells, suggesting an effect on MHC class II
presentation of MiHC in vivo. Treatment with chloroquine in vivo appears
to result in decreased CD4+ T-cell priming to MiHC and GVHD by decreased
class II MHC antigen presentation. Thus, chloroquine treatment may
represent an alternative approach to control GVHD.
DE Animal Antigen Presentation/DRUG EFFECTS B-Lymphocytes/DRUG
EFFECTS/IMMUNOLOGY Bone Marrow Transplantation/*ADVERSE
EFFECTS/*IMMUNOLOGY Chloroquine/*PHARMACOLOGY Cytotoxicity,
Immunologic/DRUG EFFECTS CD4-Positive T-Lymphocytes/DRUG
EFFECTS/IMMUNOLOGY CD8-Positive T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY
Female Graft vs Host Disease/IMMUNOLOGY/*PREVENTION & CONTROL
Histocompatibility Antigens Class II/METABOLISM Interleukin-2/BLOOD
Lymphocyte Transformation/DRUG EFFECTS Mice Mice, Inbred BALB C Mice,
Inbred C3H Mice, Inbred C57BL Minor Histocompatibility
Antigens/*METABOLISM Support, Non-U.S. Gov't T-Lymphocytes/*DRUG
EFFECTS/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).