       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).

